{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T04:08:14Z","timestamp":1788494894007,"version":"build-2803163510"},"reference-count":278,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Department of Science and Technology, Science Engineering Research Board (DST-SERB), the Government of India","award":["EEQ\/2017\/000567"],"award-info":[{"award-number":["EEQ\/2017\/000567"]}]},{"name":"BogaR Laboratories, Hyderabad"}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["Medicina"],"abstract":"<jats:p>The progression of pancreatic cancer (PC) is significantly influenced by the immune system. In the United States, PC is the third leading cause of cancer-related mortality. The high lethality of PC is attributed to its immunological advantage, which is facilitated by an immunosuppressive microenvironment, a low mutational burden, and minimal T-cell infiltration. Although immunotherapies, such as checkpoint blockades or genetically engineered T cells, have not yet demonstrated viability, there is a growing body of evidence suggesting that innovative combinations of conventional therapies and various procedures may lead to effective immunotherapy in the treatment of PC. This review focuses on the importance of the tumor microenvironment and the promising role of immunotherapies in PC.<\/jats:p>","DOI":"10.3390\/medicina61101776","type":"journal-article","created":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T09:37:21Z","timestamp":1759311441000},"page":"1776","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Tumor Microenvironment: Recent Advances in Immunotherapies of Pancreatic Cancer"],"prefix":"10.3390","volume":"61","author":[{"given":"Sharon Varghese","family":"Thankachan","sequence":"first","affiliation":[{"name":"Cancer Science Laboratory, Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur 603203, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vijayalakshmi","family":"Jayaraman","sequence":"additional","affiliation":[{"name":"Cancer Science Laboratory, Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur 603203, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liza","family":"Datta","sequence":"additional","affiliation":[{"name":"Cancer Science Laboratory, Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur 603203, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soniga","family":"Apthi","sequence":"additional","affiliation":[{"name":"Cancer Science Laboratory, Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur 603203, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Binish Fatima","family":"Zaman","sequence":"additional","affiliation":[{"name":"Cancer Science Laboratory, Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur 603203, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-6301-2758","authenticated-orcid":false,"given":"Raghav","family":"Gurunathan","sequence":"additional","affiliation":[{"name":"Cancer Science Laboratory, Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur 603203, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anuppama","family":"Suresh","sequence":"additional","affiliation":[{"name":"Cancer Science Laboratory, Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur 603203, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Parthasarathy","family":"Chandrakesan","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3568-2358","authenticated-orcid":false,"given":"Ramachandran","family":"Vinayagam","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, College of Life and Applied Sciences, Yeungnam University, 280 Daehak-Ro, Gyeongsan 38541, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang Gu","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, College of Life and Applied Sciences, Yeungnam University, 280 Daehak-Ro, Gyeongsan 38541, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2712-8333","authenticated-orcid":false,"given":"Kanagaraj","family":"Palaniyandi","sequence":"additional","affiliation":[{"name":"Cancer Science Laboratory, Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur 603203, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3708-0481","authenticated-orcid":false,"given":"Dhanavathy","family":"Gnanasampanthapandian","sequence":"additional","affiliation":[{"name":"Cancer Science Laboratory, Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur 603203, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4698","DOI":"10.3748\/wjg.v28.i32.4698","article-title":"International patterns in incidence and mortality trends of pancreatic cancer in the last three decades: A joinpoint regression analysis","volume":"28","author":"Ilic","year":"2022","journal-title":"World J. Gastroenterol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1016\/j.cell.2017.04.014","article-title":"Innate Immune Landscape in Early Lung Adenocarcinoma by Paired Single-Cell Analyses","volume":"169","author":"Lavin","year":"2017","journal-title":"Cell"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1038\/s41591-019-0382-x","article-title":"Genomic correlates of response to immune checkpoint blockade","volume":"25","author":"Keenan","year":"2019","journal-title":"Nat. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1038\/nrd.2018.97","article-title":"Targeting the NLRP3 inflammasome in inflammatory diseases","volume":"17","author":"Mangan","year":"2018","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1038\/s41577-019-0269-6","article-title":"Enhancing cancer immunotherapy with nanomedicine","volume":"20","author":"Irvine","year":"2020","journal-title":"Nat. Rev. Immunol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1111\/imr.12978","article-title":"Role of cancer-associated fibroblast subpopulations in immune infiltration, as a new means of treatment in cancer","volume":"302","author":"Mhaidly","year":"2021","journal-title":"Immunol. Rev."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Wu, L., and Zhang, X.H.-F. (2020). Tumor-Associated Neutrophils and Macrophages\u2014Heterogenous but Not Chaotic. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.553967"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1007\/s13402-016-0281-9","article-title":"The role of lymphangiogenesis and angiogenesis in tumor metastasis","volume":"39","author":"Paduch","year":"2016","journal-title":"Cell. Oncol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Poma, A.M., Torregrossa, L., Bruno, R., Basolo, F., and Fontanini, G. (2018). Hippo pathway affects survival of cancer patients: Extensive analysis of TCGA data and review of literature. Sci. Rep., 8.","DOI":"10.1038\/s41598-018-28928-3"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"3317","DOI":"10.21873\/anticanres.13474","article-title":"The Hippo Signaling Pathway in Pancreatic Cancer","volume":"39","author":"Ansari","year":"2019","journal-title":"Anticancer Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1038\/nri.2016.125","article-title":"Human immune system variation","volume":"17","author":"Brodin","year":"2017","journal-title":"Nat. Rev. Immunol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"eaat7807","DOI":"10.1126\/scitranslmed.aat7807","article-title":"The hallmarks of successful anticancer immunotherapy","volume":"10","author":"Galluzzi","year":"2018","journal-title":"Sci. Transl. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1471","DOI":"10.1016\/j.cell.2017.12.002","article-title":"CD19 CAR T Cells","volume":"171","author":"Sadelain","year":"2017","journal-title":"Cell"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1038\/nrd.2015.35","article-title":"Development of immuno-oncology drugs\u2014From CTLA4 to PD1 to the next generations","volume":"15","author":"Hoos","year":"2016","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_15","first-page":"7","article-title":"Cancer Statistics, 2017","volume":"67","author":"Siegel","year":"2017","journal-title":"CA Cancer J. Clin."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.canlet.2017.12.012","article-title":"Emerging trends in the immunotherapy of pancreatic cancer","volume":"417","author":"Banerjee","year":"2018","journal-title":"Cancer Lett."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1267","DOI":"10.1101\/gad.314617.118","article-title":"Roles of the immune system in cancer: From tumor initiation to metastatic progression","volume":"32","author":"Gonzalez","year":"2018","journal-title":"Genes. Dev."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2080","DOI":"10.1111\/cas.14069","article-title":"Regulatory T (Treg) cells in cancer: Can Treg cells be a new therapeutic target?","volume":"110","author":"Ohue","year":"2019","journal-title":"Cancer Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2128","DOI":"10.1016\/S0140-6736(18)30789-X","article-title":"International validation of the consensus Immunoscore for the classification of colon cancer: A prognostic and accuracy study","volume":"391","author":"Mlecnik","year":"2018","journal-title":"Lancet"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1016\/j.molcel.2020.05.034","article-title":"Targeting Metabolism to Improve the Tumor Microenvironment for Cancer Immunotherapy","volume":"78","author":"Bader","year":"2020","journal-title":"Mol. Cell"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1007\/978-3-319-67577-0_2","article-title":"Cancer Immunotherapy Targets Based on Understanding the T Cell-Inflamed Versus Non-T Cell-Inflamed Tumor Microenvironment","volume":"1036","author":"Gajewski","year":"2017","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1038\/nrclinonc.2017.101","article-title":"The immune contexture in cancer prognosis and treatment","volume":"14","author":"Fridman","year":"2017","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1865","DOI":"10.1158\/1078-0432.CCR-15-1507","article-title":"The Where, the When, and the How of Immune Monitoring for Cancer Immunotherapies in the Era of Checkpoint Inhibition","volume":"22","author":"Hegde","year":"2016","journal-title":"Clin. Cancer Res."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Ouyang, P., Wang, L., Wu, J., Tian, Y., Chen, C., Li, D., Yao, Z., Chen, R., Xiang, G., and Gong, J. (2024). Overcoming cold tumors: A combination strategy of immune checkpoint inhibitors. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1344272"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1042\/BST20210961","article-title":"Regulation of the antigen presentation machinery in cancer and its implication for immune surveillance","volume":"50","author":"Balasubramanian","year":"2022","journal-title":"Biochem. Soc. Trans."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"S87","DOI":"10.3747\/co.27.5223","article-title":"A review of cancer immunotherapy: From the past, to the present, to the future","volume":"27","author":"Esfahani","year":"2020","journal-title":"Curr. Oncol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.semradonc.2014.07.005","article-title":"Radiotherapy and immunogenic cell death","volume":"25","author":"Golden","year":"2015","journal-title":"Semin. Radiat. Oncol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1038\/nrclinonc.2016.60","article-title":"Cancer metabolism: A therapeutic perspective","volume":"14","author":"Pestell","year":"2017","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Kouidhi, S., Elgaaied, A.B., and Chouaib, S. (2017). Impact of Metabolism on T-Cell Differentiation and Function and Cross Talk with Tumor Microenvironment. Front. Immunol., 8.","DOI":"10.3389\/fimmu.2017.00270"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2585","DOI":"10.2353\/ajpath.2010.090899","article-title":"Role of pancreatic stellate cells in pancreatic cancer metastasis","volume":"177","author":"Xu","year":"2010","journal-title":"Am. J. Pathol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2280","DOI":"10.1016\/j.ymthe.2017.06.023","article-title":"A TIM-3 Oligonucleotide Aptamer Enhances T Cell Functions and Potentiates Tumor Immunity in Mice","volume":"25","author":"Gefen","year":"2017","journal-title":"Mol. Ther."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1038\/s41392-021-00659-4","article-title":"The molecular biology of pancreatic adenocarcinoma: Translational challenges and clinical perspectives","volume":"6","author":"Wang","year":"2021","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_33","first-page":"1937","article-title":"Tumor microenvironment in chemoresistance, metastasis and immunotherapy of pancreatic cancer","volume":"10","author":"Wang","year":"2020","journal-title":"Am. J. Cancer Res."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Bure, I.V., Nemtsova, M.V., and Zaletaev, D.V. (2019). Roles of E-cadherin and Noncoding RNAs in the Epithelial-mesenchymal Transition and Progression in Gastric Cancer. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20122870"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1186\/s12943-018-0858-1","article-title":"Tumor microenvironment participates in metastasis of pancreatic cancer","volume":"17","author":"Ren","year":"2018","journal-title":"Mol. Cancer"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.canlet.2017.03.024","article-title":"Galectin-1-driven upregulation of SDF-1 in pancreatic stellate cells promotes pancreatic cancer metastasis","volume":"397","author":"Qian","year":"2017","journal-title":"Cancer Lett."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1186\/s12943-024-02212-7","article-title":"Resistance mechanisms to immune checkpoint inhibitors: Updated insights","volume":"24","author":"Alsaafeen","year":"2025","journal-title":"Mol. Cancer"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1038\/s41571-022-00600-w","article-title":"Immune-checkpoint inhibitors: Long-term implications of toxicity","volume":"19","author":"Johnson","year":"2022","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/bjc.2017.434","article-title":"Mechanisms of resistance to immune checkpoint inhibitors","volume":"118","author":"Jenkins","year":"2018","journal-title":"Br. J. Cancer"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"3303","DOI":"10.1111\/cas.15497","article-title":"Mechanisms of resistance to immune checkpoint inhibitors","volume":"113","author":"Nagasaki","year":"2022","journal-title":"Cancer Sci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1186\/s13046-018-0981-2","article-title":"The epithelial-to-mesenchymal transition induced by tumor-associated macrophages confers chemoresistance in peritoneally disseminated pancreatic cancer","volume":"37","author":"Kuwada","year":"2018","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1186\/s12943-017-0624-9","article-title":"The epithelial to mesenchymal transition (EMT) and cancer stem cells: Implication for treatment resistance in pancreatic cancer","volume":"16","author":"Zhou","year":"2017","journal-title":"Mol. Cancer"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"e20200388","DOI":"10.1084\/jem.20200388","article-title":"Glutamine depletion regulates Slug to promote EMT and metastasis in pancreatic cancer","volume":"217","author":"Recouvreux","year":"2020","journal-title":"J. Exp. Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1038\/s41416-019-0479-5","article-title":"Tumour microenvironment of pancreatic cancer: Immune landscape is dictated by molecular and histopathological features","volume":"121","author":"Karamitopoulou","year":"2019","journal-title":"Br. J. Cancer"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1586\/17474124.2016.1117386","article-title":"The role of hypoxia in pancreatic cancer: A potential therapeutic target?","volume":"10","author":"Erkan","year":"2016","journal-title":"Expert. Rev. Gastroenterol. Hepatol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.trsl.2018.12.008","article-title":"Enhancing responsiveness of pancreatic cancer cells to gemcitabine treatment under hypoxia by heme oxygenase-1 inhibition","volume":"207","author":"Abdalla","year":"2019","journal-title":"Transl. Res."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Ahmad, I.M., Dafferner, A.J., O\u2019Connell, K.A., Mehla, K., Britigan, B.E., Hollingsworth, M.A., and Abdalla, M.Y. (2021). Heme Oxygenase-1 Inhibition Potentiates the Effects of Nab-Paclitaxel-Gemcitabine and Modulates the Tumor Microenvironment in Pancreatic Ductal Adenocarcinoma. Cancers, 13.","DOI":"10.3390\/cancers13092264"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"5123","DOI":"10.1038\/s41467-023-40727-7","article-title":"Single cell transcriptomic analyses implicate an immunosuppressive tumor microenvironment in pancreatic cancer liver metastasis","volume":"14","author":"Zhang","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_49","first-page":"284","article-title":"The Site of Lymph Node Metastasis: A Significant Prognostic Factor in Pancreatic Ductal Adenocarcinoma","volume":"38","author":"Aysal","year":"2022","journal-title":"Turk. Patoloji Derg."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/s12957-021-02478-x","article-title":"Prognosis and survival analysis of patients with pancreatic cancer: Retrospective experience of a single institution","volume":"20","author":"Li","year":"2022","journal-title":"World J. Surg. Oncol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.canlet.2015.07.048","article-title":"Notch signaling: An emerging therapeutic target for cancer treatment","volume":"369","author":"Yuan","year":"2015","journal-title":"Cancer Lett."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"739","DOI":"10.21873\/anticanres.15532","article-title":"High Incidence of Lymph-node Metastasis in a Pancreatic-cancer Patient-derived Orthotopic Xenograft (PDOX) NOG-Mouse Model","volume":"42","author":"Sugisawa","year":"2022","journal-title":"Anticancer. Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/j.canlet.2015.11.048","article-title":"The lymphatic system and pancreatic cancer","volume":"381","author":"Fink","year":"2016","journal-title":"Cancer Lett."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1186\/s13045-017-0448-5","article-title":"The role of stromal cancer-associated fibroblasts in pancreatic cancer","volume":"10","author":"Bhagat","year":"2017","journal-title":"J. Hematol. Oncol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1007\/s00424-017-1968-0","article-title":"Biology of pancreatic stellate cells-more than just pancreatic cancer","volume":"469","author":"Ferdek","year":"2017","journal-title":"Pflug. Arch."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1084\/jem.20162024","article-title":"Distinct populations of inflammatory fibroblasts and myofibroblasts in pancreatic cancer","volume":"214","author":"Biffi","year":"2017","journal-title":"J. Exp. Med."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1016\/j.trecan.2019.09.010","article-title":"CAF Subpopulations: A New Reservoir of Stromal Targets in Pancreatic Cancer","volume":"5","author":"Pereira","year":"2019","journal-title":"Trends Cancer"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1186\/s13046-019-1226-8","article-title":"Inhibition of ERK1\/2 in cancer-associated pancreatic stellate cells suppresses cancer-stromal interaction and metastasis","volume":"38","author":"Yan","year":"2019","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1006","DOI":"10.1002\/ijc.33291","article-title":"Leukemia inhibitory factor is a novel biomarker to predict lymph node and distant metastasis in pancreatic cancer","volume":"148","author":"Jiang","year":"2021","journal-title":"Int. J. Cancer"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1186\/s13046-022-02425-y","article-title":"Identification of novel early pancreatic cancer biomarkers KIF5B and SFRP2 from \u201cfirst contact\u201d interactions in the tumor microenvironment","volume":"41","author":"Signorelli","year":"2022","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1007\/s00261-017-1397-8","article-title":"Imaging findings of recurrent pancreatic cancer following resection","volume":"43","author":"Javadi","year":"2018","journal-title":"Abdom. Radiol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1186\/s13045-020-01030-w","article-title":"Targeting hypoxic tumor microenvironment in pancreatic cancer","volume":"14","author":"Tao","year":"2021","journal-title":"J. Hematol. Oncol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1038\/nrm809","article-title":"Myofibroblasts and mechano-regulation of connective tissue remodelling","volume":"3","author":"Tomasek","year":"2002","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1053\/j.gastro.2018.05.051","article-title":"NF\u03baB in Pancreatic Stellate Cells Reduces Infiltration of Tumors by Cytotoxic T Cells and Killing of Cancer Cells, via Up-regulation of CXCL12","volume":"155","author":"Garg","year":"2018","journal-title":"Gastroenterology"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"4704","DOI":"10.1172\/JCI136760","article-title":"Pancreatic ductal adenocarcinoma progression is restrained by stromal matrix","volume":"130","author":"Jiang","year":"2020","journal-title":"J. Clin. Investig."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1707","DOI":"10.1152\/physrev.00042.2019","article-title":"Microenvironmental Determinants of Pancreatic Cancer","volume":"100","author":"Hessmann","year":"2020","journal-title":"Physiol. Rev."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1007\/978-3-030-37184-5_5","article-title":"Pancreatic Stellate Cells: The Key Orchestrator of the Pancreatic Tumor Microenvironment","volume":"1234","author":"Thomas","year":"2020","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.trecan.2019.01.001","article-title":"Targeting Pancreatic Stellate Cells in Cancer","volume":"5","author":"Schnittert","year":"2019","journal-title":"Trends Cancer"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1002\/ijc.27715","article-title":"Persistent activation of pancreatic stellate cells creates a microenvironment favorable for the malignant behavior of pancreatic ductal adenocarcinoma","volume":"132","author":"Tang","year":"2013","journal-title":"Int. J. Cancer"},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Saka, D., Gokalp, M., Piyade, B., Cevik, N.C., Arik Sever, E., Unutmaz, D., Ceyhan, G.O., Demir, I.E., and Asimgil, H. (2020). Mechanisms of T-Cell Exhaustion in Pancreatic Cancer. Cancers, 12.","DOI":"10.3390\/cancers12082274"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1492","DOI":"10.1053\/j.gastro.2017.01.010","article-title":"Autophagy Is Required for Activation of Pancreatic Stellate Cells, Associated with Pancreatic Cancer Progression and Promotes Growth of Pancreatic Tumors in Mice","volume":"152","author":"Endo","year":"2017","journal-title":"Gastroenterology"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Sunami, Y., H\u00e4u\u00dfler, J., and Kleeff, J. (2020). Cellular Heterogeneity of Pancreatic Stellate Cells, Mesenchymal Stem Cells, and Cancer-Associated Fibroblasts in Pancreatic Cancer. Cancers, 12.","DOI":"10.3390\/cancers12123770"},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Piersma, B., Hayward, M.K., and Weaver, V.M. (2020). Fibrosis and cancer: A strained relationship. Biochim. Biophys. Acta Rev. Cancer, 1873.","DOI":"10.1016\/j.bbcan.2020.188356"},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Miyabayashi, K., Ijichi, H., and Fujishiro, M. (2022). The Role of the Microbiome in Pancreatic Cancer. Cancers, 14.","DOI":"10.3390\/cancers14184479"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"285","DOI":"10.7150\/jca.4537","article-title":"Analysis of pancreatic cancer microenvironment: Role of macrophage infiltrates and growth factors expression","volume":"3","author":"Gardian","year":"2012","journal-title":"J. Cancer"},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Xiang, H., Yang, R., Tu, J., Xi, Y., Yang, S., Lv, L., Zhai, X., Zhu, Y., Dong, D., and Tao, X. (2023). Metabolic reprogramming of immune cells in pancreatic cancer progression. Biomed. Pharmacother., 157.","DOI":"10.1016\/j.biopha.2022.113992"},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Huber, M., Brehm, C.U., Gress, T.M., Buchholz, M., Alashkar Alhamwe, B., von Strandmann, E.P., Slater, E.P., Bartsch, J.W., Bauer, C., and Lauth, M. (2020). The Immune Microenvironment in Pancreatic Cancer. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21197307"},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Santoni, M., Bracarda, S., Nabissi, M., Massari, F., Conti, A., Bria, E., Tortora, G., Santoni, G., and Cascinu, S. (2014). CXC and CC chemokines as angiogenic modulators in nonhaematological tumors. Biomed. Res. Int., 2014.","DOI":"10.1155\/2014\/768758"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1097\/CCO.0000000000000344","article-title":"Novel insights in the regulation and function of macrophages in the tumor microenvironment","volume":"29","author":"Bolli","year":"2017","journal-title":"Curr. Opin. Oncol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1112","DOI":"10.1136\/gutjnl-2017-313738","article-title":"Targeting both tumour-associated CXCR2+ neutrophils and CCR2+ macrophages disrupts myeloid recruitment and improves chemotherapeutic responses in pancreatic ductal adenocarcinoma","volume":"67","author":"Nywening","year":"2018","journal-title":"Gut"},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Filippini, D., Agosto, S.D., Delfino, P., Simbolo, M., Piro, G., Rusev, B., Veghini, L., Cant\u00f9, C., Lupo, F., and Ugel, S. (2019). Immunoevolution of mouse pancreatic organoid isografts from preinvasive to metastatic disease. Sci. Rep., 9.","DOI":"10.1038\/s41598-019-48663-7"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"5811","DOI":"10.1038\/s41388-018-0382-1","article-title":"Hypoxia-induced LncRNA-BX111 promotes metastasis and progression of pancreatic cancer through regulating ZEB1 transcription","volume":"37","author":"Deng","year":"2018","journal-title":"Oncogene"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1053\/j.gastro.2019.05.004","article-title":"Regulation of pH by Carbonic Anhydrase 9 Mediates Survival of Pancreatic Cancer Cells with Activated KRAS in Response to Hypoxia","volume":"157","author":"McDonald","year":"2019","journal-title":"Gastroenterology"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1006","DOI":"10.4049\/jimmunol.1400703","article-title":"Dendritic cell-derived exosomes as immunotherapies in the fight against cancer","volume":"193","author":"Pitt","year":"2014","journal-title":"J. Immunol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1038\/nm0597-558","article-title":"Induction of antitumor activity by immunization with fusions of dendritic and carcinoma cells","volume":"3","author":"Gong","year":"1997","journal-title":"Nat. Med."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"4446","DOI":"10.3748\/wjg.v22.i18.4446","article-title":"Advances in inducing adaptive immunity using cell-based cancer vaccines: Clinical applications in pancreatic cancer","volume":"22","author":"Kajihara","year":"2016","journal-title":"World J. Gastroenterol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"5323","DOI":"10.1158\/1078-0432.CCR-09-0737","article-title":"The prioritization of cancer antigens: A national cancer institute pilot project for the acceleration of translational research","volume":"15","author":"Cheever","year":"2009","journal-title":"Clin. Cancer Res."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"4795","DOI":"10.7150\/thno.30988","article-title":"Hypoxia-induced feedback of HIF-1\u03b1 and lncRNA-CF129 contributes to pancreatic cancer progression through stabilization of p53 protein","volume":"9","author":"Liu","year":"2019","journal-title":"Theranostics"},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Chen, G., Wu, K., Li, H., Xia, D., and He, T. (2022). Role of hypoxia in the tumor microenvironment and targeted therapy. Front. Oncol., 12.","DOI":"10.3389\/fonc.2022.961637"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"e000233","DOI":"10.1136\/jitc-2019-000233","article-title":"Restoration of antitumor immunity through anti-MICA antibodies elicited with a chimeric protein","volume":"8","author":"Torres","year":"2020","journal-title":"J. Immunother. Cancer"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"265","DOI":"10.2174\/157489212801820020","article-title":"Carcinoembryonic antigen (CEA)-based cancer vaccines: Recent patents and antitumor effects from experimental models to clinical trials","volume":"7","author":"Turriziani","year":"2012","journal-title":"Recent. Pat. Anticancer. Drug Discov."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1002\/jcla.1860050510","article-title":"Carcinoembryonic antigen gene family: Molecular biology and clinical perspectives","volume":"5","author":"Thompson","year":"1991","journal-title":"J. Clin. Lab. Anal."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1053\/j.gastro.2011.12.042","article-title":"Presence of somatic mutations in most early-stage pancreatic intraepithelial neoplasia","volume":"142","author":"Kanda","year":"2012","journal-title":"Gastroenterology"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1038\/s41575-020-0300-1","article-title":"Pancreatic cancer stroma: An update on therapeutic targeting strategies","volume":"17","author":"Hosein","year":"2020","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1097\/MPA.0b013e3182148342","article-title":"Pattern of lymph node metastasis spread in pancreatic cancer","volume":"40","author":"Kanda","year":"2011","journal-title":"Pancreas"},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Riabov, V., Gudima, A., Wang, N., Mickley, A., Orekhov, A., and Kzhyshkowska, J. (2014). Role of tumor associated macrophages in tumor angiogenesis and lymphangiogenesis. Front. Physiol., 5.","DOI":"10.3389\/fphys.2014.00075"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1120","DOI":"10.1002\/ijc.25449","article-title":"Long-term follow-up of patients with resected pancreatic cancer following vaccination against mutant K-ras","volume":"128","author":"Weden","year":"2011","journal-title":"Int. J. Cancer"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"3578","DOI":"10.1158\/1078-0432.CCR-19-3978","article-title":"Evaluation of Cyclophosphamide\/GVAX Pancreas Followed by Listeria-Mesothelin (CRS-207) with or without Nivolumab in Patients with Pancreatic Cancer","volume":"26","author":"Tsujikawa","year":"2020","journal-title":"Clin. Cancer Res."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.1016\/j.biopha.2018.09.136","article-title":"Role of angiogenesis in pancreatic cancer biology and therapy","volume":"108","author":"Zhang","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1038\/s41392-020-00359-5","article-title":"Exosome-mediated metabolic reprogramming: The emerging role in tumor microenvironment remodeling and its influence on cancer progression","volume":"5","author":"Yang","year":"2020","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1126\/science.aai8515","article-title":"Origins of lymphatic and distant metastases in human colorectal cancer","volume":"357","author":"Naxerova","year":"2017","journal-title":"Science"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.ceb.2015.06.007","article-title":"Filopodia in cell adhesion, 3D migration and cancer cell invasion","volume":"36","author":"Jacquemet","year":"2015","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"5493","DOI":"10.1158\/1078-0432.CCR-18-2992","article-title":"Results from a Phase IIb, Randomized, Multicenter Study of GVAX Pancreas and CRS-207 Compared with Chemotherapy in Adults with Previously Treated Metastatic Pancreatic Adenocarcinoma (ECLIPSE Study)","volume":"25","author":"Le","year":"2019","journal-title":"Clin. Cancer Res."},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Bassani-Sternberg, M., Digklia, A., Huber, F., Wagner, D., Sempoux, C., Stevenson, B.J., Thierry, A.C., Michaux, J., Pak, H., and Racle, J. (2019). A Phase Ib Study of the Combination of Personalized Autologous Dendritic Cell Vaccine, Aspirin, and Standard of Care Adjuvant Chemotherapy Followed by Nivolumab for Resected Pancreatic Adenocarcinoma-A Proof of Antigen Discovery Feasibility in Three Patients. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.01832"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"e27878","DOI":"10.4161\/onci.27878","article-title":"Trial Watch: Chemotherapy with immunogenic cell death inducers","volume":"3","author":"Vacchelli","year":"2014","journal-title":"Oncoimmunology"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"3005","DOI":"10.1111\/cas.13738","article-title":"Heterogeneity of tumor lymphangiogenesis: Progress and prospects","volume":"109","author":"Hu","year":"2018","journal-title":"Cancer Sci."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1186\/s40425-016-0164-7","article-title":"Expansion of tumor-infiltrating lymphocytes (TIL) from human pancreatic tumors","volume":"4","author":"Hall","year":"2016","journal-title":"J. Immunother. Cancer"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1101\/gr.238121.118","article-title":"The circular RNome of primary breast cancer","volume":"29","author":"Smid","year":"2019","journal-title":"Genome Res."},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"Meng, Q., Valentini, D., Rao, M., and Maeurer, M. (2018). KRAS RENAISSANCE(S) in Tumor Infiltrating B Cells in Pancreatic Cancer. Front. Oncol., 8.","DOI":"10.3389\/fonc.2018.00384"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1038\/s41423-020-00565-9","article-title":"Tumor-infiltrating lymphocytes in the immunotherapy era","volume":"18","author":"Paijens","year":"2021","journal-title":"Cell. Mol. Immunol."},{"key":"ref_111","doi-asserted-by":"crossref","unstructured":"Parrot, T., Oger, R., Allard, M., Desfran\u00e7ois, J., Raingeard de la Bl\u00e9ti\u00e8re, D., Coutolleau, A., Preisser, L., Khammari, A., Dr\u00e9no, B., and Delneste, Y. (2020). Transcriptomic features of tumour-infiltrating CD4lowCD8high double positive \u03b1\u03b2 T cells in melanoma. Sci. Rep., 10.","DOI":"10.1038\/s41598-020-62664-x"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"4297","DOI":"10.1038\/s41467-018-06653-9","article-title":"Human breast tumor-infiltrating CD8+ T cells retain polyfunctionality despite PD-1 expression","volume":"9","author":"Egelston","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/j.immuni.2017.01.009","article-title":"CD49a Expression Defines Tissue-Resident CD8+ T Cells Poised for Cytotoxic Function in Human Skin","volume":"46","author":"Cheuk","year":"2017","journal-title":"Immunity"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"2451","DOI":"10.4049\/jimmunol.1700571","article-title":"Chemokine Receptor-Dependent Control of Skin Tissue-Resident Memory T Cell Formation","volume":"199","author":"Zaid","year":"2017","journal-title":"J. Immunol."},{"key":"ref_115","doi-asserted-by":"crossref","unstructured":"Oja, A.E., Piet, B., van der Zwan, D., Blaauwgeers, H., Mensink, M., de Kivit, S., Borst, J., Nolte, M.A., van Lier, R.A.W., and Stark, R. (2018). Functional Heterogeneity of CD4+ Tumor-Infiltrating Lymphocytes with a Resident Memory Phenotype in NSCLC. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.02654"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.1002\/ijc.30138","article-title":"Prognostic impact of tumour-infiltrating B cells and plasma cells in colorectal cancer","volume":"139","author":"Berntsson","year":"2016","journal-title":"Int. J. Cancer"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.immuni.2019.11.014","article-title":"Immune Landscape of Viral- and Carcinogen-Driven Head and Neck Cancer","volume":"52","author":"Cillo","year":"2020","journal-title":"Immunity"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"e129641","DOI":"10.1172\/jci.insight.129641","article-title":"Tumor infiltrating B-cells signal functional humoral immune responses in breast cancer","volume":"5","author":"Garaud","year":"2019","journal-title":"JCI Insight"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1038\/s41586-019-1922-8","article-title":"B cells and tertiary lymphoid structures promote immunotherapy response","volume":"577","author":"Helmink","year":"2020","journal-title":"Nature"},{"key":"ref_120","doi-asserted-by":"crossref","unstructured":"Senturk, Z.N., Akdag, I., Deniz, B., and Sayi-Yazgan, A. (2023). Pancreatic cancer: Emerging field of regulatory B-cell-targeted immunotherapies. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1152551"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1158\/2159-8290.CD-15-0843","article-title":"IL35-Producing B Cells Promote the Development of Pancreatic Neoplasia","volume":"6","author":"Das","year":"2016","journal-title":"Cancer Discov."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1111\/imr.12859","article-title":"The role of B cell antigen presentation in the initiation of CD4+ T cell response","volume":"296","author":"Hua","year":"2020","journal-title":"Immunol. Rev."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1016\/j.ccell.2022.04.011","article-title":"Mesothelial cell-derived antigen-presenting cancer-associated fibroblasts induce expansion of regulatory T cells in pancreatic cancer","volume":"40","author":"Huang","year":"2022","journal-title":"Cancer Cell"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1016\/j.immuni.2018.08.012","article-title":"B Cells Are the Dominant Antigen-Presenting Cells that Activate Naive CD4+ T Cells upon Immunization with a Virus-Derived Nanoparticle Antigen","volume":"49","author":"Hong","year":"2018","journal-title":"Immunity"},{"key":"ref_125","doi-asserted-by":"crossref","unstructured":"Thyagarajan, A., Alshehri, M.S.A., Miller, K.L.R., Sherwin, C.M., Travers, J.B., and Sahu, R.P. (2019). Myeloid-Derived Suppressor Cells and Pancreatic Cancer: Implications in Novel Therapeutic Approaches. Cancers, 11.","DOI":"10.3390\/cancers11111627"},{"key":"ref_126","doi-asserted-by":"crossref","unstructured":"Mota Reyes, C., Demir, E., Cifcibasi, K., Istvanffy, R., Friess, H., and Demir, I.E. (2022). Regulatory T Cells in Pancreatic Cancer: Of Mice and Men. Cancers, 14.","DOI":"10.3390\/cancers14194582"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"3354","DOI":"10.4161\/hv.34392","article-title":"Pancreatic cancer: Role of the immune system in cancer progression and vaccine-based immunotherapy","volume":"10","author":"Amedei","year":"2014","journal-title":"Hum. Vaccin. Immunother."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1054\/bjoc.2000.1423","article-title":"Inhibition of transcription factor nuclear factor-kappaB by a mutant inhibitor-kappaBalpha attenuates resistance of human head and neck squamous cell carcinoma to TNF-alpha caspase-mediated cell death","volume":"83","author":"Duffey","year":"2000","journal-title":"Br. J. Cancer"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1002\/biof.107","article-title":"Cytokine regulation of natural killer cell effector functions","volume":"36","author":"Zwirner","year":"2010","journal-title":"Biofactors"},{"key":"ref_130","doi-asserted-by":"crossref","unstructured":"Sadozai, H., Acharjee, A., Eppenberger-Castori, S., Gloor, B., Gruber, T., Schenk, M., and Karamitopoulou, E. (2021). Distinct Stromal and Immune Features Collectively Contribute to Long-Term Survival in Pancreatic Cancer. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.643529"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.jare.2020.03.009","article-title":"The landscape of immune cell infiltration and its clinical implications of pancreatic ductal adenocarcinoma","volume":"24","author":"Xu","year":"2020","journal-title":"J. Adv. Res."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1007\/s44272-023-00005-5","article-title":"The role of innate immune cells as modulators of the tumor microenvironment in the metastasis and treatment of pancreatic cancer","volume":"2","author":"Zhu","year":"2023","journal-title":"Clin. Cancer Bull."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"5439","DOI":"10.1038\/s41467-020-19288-6","article-title":"Immune modulatory effects of oncogenic KRAS in cancer","volume":"11","author":"Hamarsheh","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_134","doi-asserted-by":"crossref","unstructured":"Wang, C., Tan, J.Y.M., Chitkara, N., and Bhatt, S. (2024). TP53 Mutation-Mediated Immune Evasion in Cancer: Mechanisms and Therapeutic Implications. Cancers, 16.","DOI":"10.3390\/cancers16173069"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"607","DOI":"10.2217\/imt-2016-0142","article-title":"Immunotherapy for pancreatic cancer: Present and future","volume":"9","author":"Aroldi","year":"2017","journal-title":"Immunotherapy"},{"key":"ref_136","first-page":"154","article-title":"The toxins of William B. Coley and the treatment of bone and soft-tissue sarcomas","volume":"26","author":"McCarthy","year":"2006","journal-title":"Iowa Orthop. J."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1038\/s41573-018-0006-z","article-title":"Delivery technologies for cancer immunotherapy","volume":"18","author":"Riley","year":"2019","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"5451","DOI":"10.4049\/jimmunol.1490019","article-title":"IL-2: The first effective immunotherapy for human cancer","volume":"192","author":"Rosenberg","year":"2014","journal-title":"J. Immunol."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.ejca.2017.01.035","article-title":"Cancer immunotherapy: Opportunities and challenges in the rapidly evolving clinical landscape","volume":"81","author":"Emens","year":"2017","journal-title":"Eur. J. Cancer"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"e007586","DOI":"10.1136\/jitc-2023-007586","article-title":"Multicenter randomized controlled trial of neoadjuvant chemoradiotherapy alone or in combination with pembrolizumab in patients with resectable or borderline resectable pancreatic adenocarcinoma","volume":"11","author":"Katz","year":"2023","journal-title":"J. Immunother. Cancer"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"4024","DOI":"10.1200\/JCO.2023.41.16_suppl.4024","article-title":"Preliminary translational immune and stromal correlates in a randomized phase II trial of pembrolizumab with or without defactinib for resectable pancreatic ductal adenocarcinoma (PDAC)","volume":"41","author":"Abbas","year":"2023","journal-title":"J. Clin. Oncol."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1038\/nature25459","article-title":"Evolutionary routes and KRAS dosage define pancreatic cancer phenotypes","volume":"554","author":"Mueller","year":"2018","journal-title":"Nature"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"1020","DOI":"10.1001\/jamaoncol.2019.0892","article-title":"Total Neoadjuvant Therapy with FOLFIRINOX in Combination with Losartan Followed by Chemoradiotherapy for Locally Advanced Pancreatic Cancer: A Phase 2 Clinical Trial","volume":"5","author":"Murphy","year":"2019","journal-title":"JAMA Oncol."},{"key":"ref_144","doi-asserted-by":"crossref","unstructured":"Chick, R.C., Gunderson, A.J., Rahman, S., and Cloyd, J.M. (2023). Neoadjuvant Immunotherapy for Localized Pancreatic Cancer: Challenges and Early Results. Cancers, 15.","DOI":"10.3390\/cancers15153967"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"3871","DOI":"10.3390\/curroncol30040293","article-title":"Pancreatic Ductal Adenocarcinoma and Immune Checkpoint Inhibitors: The Gray Curtain of Immunotherapy and Spikes of Lights","volume":"30","author":"Balsano","year":"2023","journal-title":"Curr. Oncol."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"eadk1827","DOI":"10.1126\/sciadv.adk1827","article-title":"Neoadjuvant radioimmunotherapy in pancreatic cancer enhances effector T cell infiltration and shortens their distances to tumor cells","volume":"10","author":"Wang","year":"2024","journal-title":"Sci. Adv."},{"key":"ref_147","first-page":"699","article-title":"The tumor microenvironment of pancreatic adenocarcinoma and immune checkpoint inhibitor resistance: A perplex relationship","volume":"3","author":"Sahin","year":"2020","journal-title":"Cancer Drug Resist."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"5071","DOI":"10.1245\/s10434-023-13383-w","article-title":"Sintilimab Plus Modified FOLFIRINOX in Metastatic or Recurrent Pancreatic Cancer: The Randomized Phase II CISPD3 Trial","volume":"30","author":"Fu","year":"2023","journal-title":"Ann. Surg. Oncol."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1007\/s00262-024-03821-3","article-title":"Adding-on nivolumab to chemotherapy-stabilized patients is associated with improved survival in advanced pancreatic ductal adenocarcinoma","volume":"73","author":"Yang","year":"2024","journal-title":"Cancer Immunol. Immunother."},{"key":"ref_150","doi-asserted-by":"crossref","unstructured":"Olaoba, O.T., Yang, M., Adelusi, T.I., Maidens, T., Kimchi, E.T., Staveley-O\u2019Carroll, K.F., and Li, G. (2024). Targeted Therapy for Highly Desmoplastic and Immunosuppressive Tumor Microenvironment of Pancreatic Ductal Adenocarcinoma. Cancers, 16.","DOI":"10.3390\/cancers16081470"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"2270","DOI":"10.1158\/1538-7445.AM2023-2270","article-title":"Abstract 2270: Combination of CXCR4 antagonist and anti-PD1 therapy results in significant mobilization and increased infiltration of myeloid cells into the metastatic liver microenvironment of PDAC","volume":"83","author":"Shin","year":"2023","journal-title":"Cancer Res."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1016\/S1470-2045(22)00369-2","article-title":"Niraparib plus nivolumab or niraparib plus ipilimumab in patients with platinum-sensitive advanced pancreatic cancer: A randomised, phase 1b\/2 trial","volume":"23","author":"Reiss","year":"2022","journal-title":"Lancet Oncol."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"S139","DOI":"10.1016\/j.annonc.2024.05.474","article-title":"331P Phase Ib\/IIa study to evaluate safety and efficacy of priming treatment with the hedgehog inhibitor NLM-001 prior to gemcitabine and nab-paclitaxel plus zalifrelimab as first-line treatment in patients with advanced pancreatic cancer: NUMANTIA study","volume":"35","author":"McAndrews","year":"2024","journal-title":"Ann. Oncol."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"e179292","DOI":"10.1172\/jci.insight.179292","article-title":"Phosphodiesterase-5 inhibition collaborates with vaccine-based immunotherapy to reprogram myeloid cells in pancreatic ductal adenocarcinoma","volume":"9","author":"Gross","year":"2024","journal-title":"JCI Insight"},{"key":"ref_155","first-page":"15","article-title":"Combination of modified FOLFIRINOX with stereotactic body radiotherapy as an induction therapy for locally advanced pancreatic adenocarcinoma\u2014A prospective single-arm study","volume":"28","author":"Piatek","year":"2024","journal-title":"Contemp. Oncol."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"102016","DOI":"10.1016\/j.ctrv.2020.102016","article-title":"Immunotherapy for pancreatic cancer: A 2020 update","volume":"86","author":"Schizas","year":"2020","journal-title":"Cancer Treat. Rev."},{"key":"ref_157","doi-asserted-by":"crossref","unstructured":"Foucher, E.D., Ghigo, C., Chouaib, S., Galon, J., Iovanna, J., and Olive, D. (2018). Pancreatic Ductal Adenocarcinoma: A Strong Imbalance of Good and Bad Immunological Cops in the Tumor Microenvironment. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.01044"},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1038\/s41423-020-0488-6","article-title":"The history and advances in cancer immunotherapy: Understanding the characteristics of tumor-infiltrating immune cells and their therapeutic implications","volume":"17","author":"Zhang","year":"2020","journal-title":"Cell. Mol. Immunol."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1056\/NEJMoa1709684","article-title":"Overall Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma","volume":"377","author":"Wolchok","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"250","DOI":"10.20517\/2394-4722.2017.41","article-title":"Cancer immunotherapy: A brief review of the history, possibilities, and challenges ahead","volume":"3","author":"Oiseth","year":"2017","journal-title":"J. Cancer Metastasis Treat."},{"key":"ref_161","doi-asserted-by":"crossref","unstructured":"Farkona, S., Diamandis, E.P., and Blasutig, I.M. (2016). Cancer immunotherapy: The beginning of the end of cancer?. BMC Med., 14.","DOI":"10.1186\/s12916-016-0623-5"},{"key":"ref_162","doi-asserted-by":"crossref","unstructured":"Sureban, S.M., Berahovich, R., Zhou, H., Xu, S., Wu, L., Ding, K., May, R., Qu, D., Bannerman-Menson, E., and Golubovskaya, V. (2019). DCLK1 Monoclonal Antibody-Based CAR-T Cells as a Novel Treatment Strategy against Human Colorectal Cancers. Cancers, 12.","DOI":"10.3390\/cancers12010054"},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1186\/s13046-022-02273-w","article-title":"Combination therapy for pancreatic cancer: Anti-PD-(L)1-based strategy","volume":"41","author":"Liu","year":"2022","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"6864","DOI":"10.3390\/curroncol29100541","article-title":"The Role of Immunotherapy in Pancreatic Cancer","volume":"29","author":"Mukherji","year":"2022","journal-title":"Curr. Oncol."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.canlet.2017.08.006","article-title":"PD-1\/PD-L1 and immunotherapy for pancreatic cancer","volume":"407","author":"Feng","year":"2017","journal-title":"Cancer Lett."},{"key":"ref_166","doi-asserted-by":"crossref","unstructured":"Akce, M., Zaidi, M.Y., Waller, E.K., El-Rayes, B.F., and Lesinski, G.B. (2018). The Potential of CAR T Cell Therapy in Pancreatic Cancer. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.02166"},{"key":"ref_167","doi-asserted-by":"crossref","unstructured":"Chulpanova, D.S., Kitaeva, K.V., Green, A.R., Rizvanov, A.A., and Solovyeva, V.V. (2020). Molecular Aspects and Future Perspectives of Cytokine-Based Anti-cancer Immunotherapy. Front. Cell Dev. Biol., 8.","DOI":"10.3389\/fcell.2020.00402"},{"key":"ref_168","doi-asserted-by":"crossref","unstructured":"Cao, Z., Weygant, N., Chandrakesan, P., Houchen, C.W., Peng, J., and Qu, D. (2020). Tuft and Cancer Stem Cell Marker DCLK1: A New Target to Enhance Anti-Tumor Immunity in the Tumor Microenvironment. Cancers, 12.","DOI":"10.3390\/cancers12123801"},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"104118","DOI":"10.1016\/j.critrevonc.2023.104118","article-title":"DCLK1 and tuft cells: Immune-related functions and implications for cancer immunotherapy","volume":"191","author":"Ding","year":"2023","journal-title":"Crit. Rev. Oncol. Hematol."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/bs.pmbts.2019.03.006","article-title":"Immunotherapy of pancreatic cancer","volume":"164","author":"Sunami","year":"2019","journal-title":"Prog. Mol. Biol. Transl. Sci."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"2112","DOI":"10.1056\/NEJMoa2119662","article-title":"Neoantigen T-Cell Receptor Gene Therapy in Pancreatic Cancer","volume":"386","author":"Leidner","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.pharmthera.2016.06.010","article-title":"Chimeric antigen receptor-modified T cells for the treatment of solid tumors: Defining the challenges and next steps","volume":"166","author":"Beatty","year":"2016","journal-title":"Pharmacol. Ther."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1136\/gutjnl-2016-312288","article-title":"Management of Helicobacter pylori infection-the Maastricht V\/Florence Consensus Report","volume":"66","author":"Malfertheiner","year":"2017","journal-title":"Gut"},{"key":"ref_174","doi-asserted-by":"crossref","unstructured":"Zahavi, D., and Weiner, L. (2020). Monoclonal Antibodies in Cancer Therapy. Antibodies, 9.","DOI":"10.3390\/antib9030034"},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1186\/s40425-018-0448-1","article-title":"Acquired resistance to immunotherapy in MMR-D pancreatic cancer","volume":"6","author":"Hu","year":"2018","journal-title":"J. Immunother. Cancer"},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"878","DOI":"10.1038\/s41591-020-0880-x","article-title":"BL-8040, a CXCR4 antagonist, in combination with pembrolizumab and chemotherapy for pancreatic cancer: The COMBAT trial","volume":"26","author":"Bockorny","year":"2020","journal-title":"Nat. Med."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1016\/j.immuni.2015.11.024","article-title":"Immunogenic Chemotherapy Sensitizes Tumors to Checkpoint Blockade Therapy","volume":"44","author":"Pfirschke","year":"2016","journal-title":"Immunity"},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"1748","DOI":"10.1158\/2326-6066.CIR-19-0107","article-title":"Direct Detection and Quantification of Neoantigens","volume":"7","author":"Wang","year":"2019","journal-title":"Cancer Immunol. Res."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1146\/annurev-cancerbio-030518-055636","article-title":"Roles of the cGAS-STING Pathway in Cancer Immunosurveillance and Immunotherapy","volume":"3","author":"Yum","year":"2019","journal-title":"Annu. Rev. Cancer Biol."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"4282","DOI":"10.1158\/0008-5472.CAN-17-3821","article-title":"Radiotherapy and CD40 Activation Separately Augment Immunity to Checkpoint Blockade in Cancer","volume":"78","author":"Rech","year":"2018","journal-title":"Cancer Res."},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1016\/j.ccell.2020.08.004","article-title":"Challenges and Opportunities for Pancreatic Cancer Immunotherapy","volume":"38","author":"Bear","year":"2020","journal-title":"Cancer Cell"},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"15618","DOI":"10.1038\/ncomms15618","article-title":"DNA exonuclease Trex1 regulates radiotherapy-induced tumour immunogenicity","volume":"8","author":"Alard","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"e122092","DOI":"10.1172\/jci.insight.122092","article-title":"T cell receptor repertoire features associated with survival in immunotherapy-treated pancreatic ductal adenocarcinoma","volume":"3","author":"Hopkins","year":"2018","journal-title":"JCI Insight"},{"key":"ref_184","doi-asserted-by":"crossref","unstructured":"Curran, M.A., Kim, M., Montalvo, W., Al-Shamkhani, A., and Allison, J.P. (2011). Combination CTLA-4 Blockade and 4-1BB Activation Enhances Tumor Rejection by Increasing T-Cell Infiltration, Proliferation, and Cytokine Production. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0019499"},{"key":"ref_185","doi-asserted-by":"crossref","unstructured":"Zahavi, D., and Hodge, J.W. (2023). Targeting Immunosuppressive Adenosine Signaling: A Review of Potential Immunotherapy Combination Strategies. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24108871"},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"3529","DOI":"10.2147\/DDDT.S60328","article-title":"Pancreatic cancer: Optimizing treatment options, new, and emerging targeted therapies","volume":"9","author":"Chiorean","year":"2015","journal-title":"Drug Des. Devel Ther."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"990","DOI":"10.1158\/2326-6066.CIR-18-0277","article-title":"T Cell-Inflamed versus Non-T Cell-Inflamed Tumors: A Conceptual Framework for Cancer Immunotherapy Drug Development and Combination Therapy Selection","volume":"6","author":"Trujillo","year":"2018","journal-title":"Cancer Immunol. Res."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1136\/gutjnl-2016-312078","article-title":"Myeloid cells are required for PD-1\/PD-L1 checkpoint activation and the establishment of an immunosuppressive environment in pancreatic cancer","volume":"66","author":"Zhang","year":"2017","journal-title":"Gut"},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1038\/s41392-021-00769-z","article-title":"Pancreatic cancer cells render tumor-associated macrophages metabolically reprogrammed by a GARP and DNA methylation-mediated mechanism","volume":"6","author":"Zhang","year":"2021","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12964-023-01388-7","article-title":"Macrophages reprogramming driven by cancer-associated fibroblasts under FOLFIRINOX treatment correlates with shorter survival in pancreatic cancer","volume":"22","author":"Hussain","year":"2024","journal-title":"Cell Commun. Signal"},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"4828","DOI":"10.1200\/JCO.2011.38.0899","article-title":"Cancer immunotherapy comes of age","volume":"29","author":"Topalian","year":"2011","journal-title":"J. Clin. Oncol."},{"key":"ref_192","doi-asserted-by":"crossref","unstructured":"Tsang, K.Y., Fantini, M., Mavroukakis, S.A., Zaki, A., Annunziata, C.M., and Arlen, P.M. (2022). Development and Characterization of an Anti-Cancer Monoclonal Antibody for Treatment of Human Carcinomas. Cancers, 14.","DOI":"10.3390\/cancers14133037"},{"key":"ref_193","doi-asserted-by":"crossref","unstructured":"Hafeez, U., Parakh, S., Gan, H.K., and Scott, A.M. (2020). Antibody-Drug Conjugates for Cancer Therapy. Molecules, 25.","DOI":"10.3390\/molecules25204764"},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1146\/annurev.immunol.16.1.111","article-title":"CD40 and CD154 in cell-mediated immunity","volume":"16","author":"Grewal","year":"1998","journal-title":"Annu. Rev. Immunol."},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1038\/30996","article-title":"Help for cytotoxic-T-cell responses is mediated by CD40 signalling","volume":"393","author":"Bennett","year":"1998","journal-title":"Nature"},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.ctrv.2019.06.005","article-title":"Checkpoint inhibitors in pancreatic cancer","volume":"78","author":"Henriksen","year":"2019","journal-title":"Cancer Treat. Rev."},{"key":"ref_197","doi-asserted-by":"crossref","unstructured":"Chen, S.H., Hung, W.C., Wang, P., Paul, C., and Konstantopoulos, K. (2013). Mesothelin binding to CA125\/MUC16 promotes pancreatic cancer cell motility and invasion via MMP-7 activation. Sci. Rep., 3.","DOI":"10.1038\/srep01870"},{"key":"ref_198","doi-asserted-by":"crossref","unstructured":"Marshall, H.T., and Djamgoz, M.B.A. (2018). Immuno-Oncology: Emerging Targets and Combination Therapies. Front. Oncol., 8.","DOI":"10.3389\/fonc.2018.00315"},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1016\/j.jconrel.2020.08.021","article-title":"Antibody and antibody fragments for cancer immunotherapy","volume":"328","author":"Chen","year":"2020","journal-title":"J. Control Release"},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"6","DOI":"10.21037\/tgh.2020.04.03","article-title":"Pancreatic cancer and immune checkpoint inhibitors-still a long way to go","volume":"6","author":"Bian","year":"2021","journal-title":"Transl. Gastroenterol. Hepatol."},{"key":"ref_201","doi-asserted-by":"crossref","unstructured":"Tran, L.C., Ozdemir, B.C., and Berger, M.D. (2023). The Role of Immune Checkpoint Inhibitors in Metastatic Pancreatic Cancer: Current State and Outlook. Pharmaceuticals, 16.","DOI":"10.3390\/ph16101411"},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1038\/nrclinonc.2015.209","article-title":"Combination cancer immunotherapies tailored to the tumour microenvironment","volume":"13","author":"Smyth","year":"2016","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1186\/s12943-020-01151-3","article-title":"Current advances and outlooks in immunotherapy for pancreatic ductal adenocarcinoma","volume":"19","author":"Fan","year":"2020","journal-title":"Mol. Cancer"},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1093\/intimm\/dxab077","article-title":"T-cell-intrinsic and -extrinsic regulation of PD-1 function","volume":"33","author":"Sugiura","year":"2021","journal-title":"Int. Immunol."},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1016\/j.ccell.2015.10.012","article-title":"Immunological Effects of Conventional Chemotherapy and Targeted Anticancer Agents","volume":"28","author":"Galluzzi","year":"2015","journal-title":"Cancer Cell"},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"1307","DOI":"10.2217\/imt-2022-0196","article-title":"Safety and efficacy analysis of PD-1 inhibitors in combination with chemotherapy for advanced pancreatic cancer","volume":"14","author":"Song","year":"2022","journal-title":"Immunotherapy"},{"key":"ref_207","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1158\/2326-6066.CIR-14-0027","article-title":"Immunotherapy converts nonimmunogenic pancreatic tumors into immunogenic foci of immune regulation","volume":"2","author":"Lutz","year":"2014","journal-title":"Cancer Immunol. Res."},{"key":"ref_208","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1084\/jem.182.2.283","article-title":"The endocytic activity of dendritic cells","volume":"182","author":"Steinman","year":"1995","journal-title":"J. Exp. Med."},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1016\/j.celrep.2017.06.062","article-title":"Crosstalk between Regulatory T Cells and Tumor-Associated Dendritic Cells Negates Anti-tumor Immunity in Pancreatic Cancer","volume":"20","author":"Jang","year":"2017","journal-title":"Cell Rep."},{"key":"ref_210","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1007\/s10238-011-0159-0","article-title":"A phase I pilot trial of MUC1-peptide-pulsed dendritic cells in the treatment of advanced pancreatic cancer","volume":"12","author":"Rong","year":"2012","journal-title":"Clin. Exp. Med."},{"key":"ref_211","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1186\/s13063-019-3332-5","article-title":"A double-blind randomized comparative clinical trial to evaluate the safety and efficacy of dendritic cell vaccine loaded with WT1 peptides (TLP0-001) in combination with S-1 in patients with advanced pancreatic cancer refractory to standard chemotherapy","volume":"20","author":"Katsuda","year":"2019","journal-title":"Trials"},{"key":"ref_212","doi-asserted-by":"crossref","first-page":"2969","DOI":"10.12998\/wjcc.v9.i13.2969","article-title":"Immunotherapy for pancreatic cancer","volume":"9","author":"Yoon","year":"2021","journal-title":"World J. Clin. Cases"},{"key":"ref_213","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1038\/nrc1252","article-title":"Cytokines in cancer pathogenesis and cancer therapy","volume":"4","author":"Dranoff","year":"2004","journal-title":"Nat. Rev. Cancer"},{"key":"ref_214","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1053\/j.seminoncol.2015.05.015","article-title":"Anticancer Cytokines: Biology and Clinical Effects of Interferon-alpha2, Interleukin (IL)-2, IL-15, IL-21, and IL-12","volume":"42","author":"Floros","year":"2015","journal-title":"Semin. Oncol."},{"key":"ref_215","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1158\/2326-6066.CIR-17-0495","article-title":"Targeting Cytokine Therapy to the Pancreatic Tumor Microenvironment Using PD-L1-Specific VHHs","volume":"6","author":"Dougan","year":"2018","journal-title":"Cancer Immunol. Res."},{"key":"ref_216","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1080\/21645515.2017.1412896","article-title":"Talimogene laherparepvec: First in class oncolytic virotherapy","volume":"14","author":"Conry","year":"2018","journal-title":"Hum. Vaccin. Immunother."},{"key":"ref_217","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/j.hoc.2018.12.004","article-title":"Cytokine Therapy","volume":"33","author":"Silk","year":"2019","journal-title":"Hematol. Oncol. Clin. North Am."},{"key":"ref_218","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.semcancer.2017.10.001","article-title":"Emerging targets in cancer immunotherapy","volume":"52","author":"Burugu","year":"2018","journal-title":"Semin. Cancer Biol."},{"key":"ref_219","doi-asserted-by":"crossref","first-page":"S1581","DOI":"10.21037\/jtd.2018.02.79","article-title":"Next generation immune-checkpoints for cancer therapy","volume":"10","author":"Donini","year":"2018","journal-title":"J. Thorac. Dis."},{"key":"ref_220","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1186\/s13045-018-0582-8","article-title":"Next generation of immune checkpoint therapy in cancer: New developments and challenges","volume":"11","author":"Dholaria","year":"2018","journal-title":"J. Hematol. Oncol."},{"key":"ref_221","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1007\/s13402-022-00741-1","article-title":"Immunosuppression, immune escape, and immunotherapy in pancreatic cancer: Focused on the tumor microenvironment","volume":"46","author":"Zhu","year":"2023","journal-title":"Cell. Oncol."},{"key":"ref_222","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.1111\/cas.12986","article-title":"Lymphocyte-activation gene-3, an important immune checkpoint in cancer","volume":"107","author":"He","year":"2016","journal-title":"Cancer Sci."},{"key":"ref_223","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1038\/s41577-020-0306-5","article-title":"A guide to cancer immunotherapy: From T cell basic science to clinical practice","volume":"20","author":"Waldman","year":"2020","journal-title":"Nat. Rev. Immunol."},{"key":"ref_224","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1016\/j.immuni.2016.05.001","article-title":"Lag-3, Tim-3, and TIGIT: Co-inhibitory Receptors with Specialized Functions in Immune Regulation","volume":"44","author":"Anderson","year":"2016","journal-title":"Immunity"},{"key":"ref_225","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1042\/CS20181003","article-title":"Immunotherapy: Enhancing the efficacy of this promising therapeutic in multiple cancers","volume":"133","author":"Inthagard","year":"2019","journal-title":"Clin. Sci."},{"key":"ref_226","doi-asserted-by":"crossref","first-page":"1540","DOI":"10.1016\/S0140-6736(15)01281-7","article-title":"Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): A randomised controlled trial","volume":"387","author":"Herbst","year":"2016","journal-title":"Lancet"},{"key":"ref_227","doi-asserted-by":"crossref","unstructured":"Qiao, G., Chen, M., Bucsek, M.J., Repasky, E.A., and Hylander, B.L. (2018). Adrenergic Signaling: A Targetable Checkpoint Limiting Development of the Antitumor Immune Response. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.00164"},{"key":"ref_228","doi-asserted-by":"crossref","first-page":"1600","DOI":"10.1182\/blood.V90.4.1600","article-title":"Role of A2a extracellular adenosine receptor-mediated signaling in adenosine-mediated inhibition of T-cell activation and expansion","volume":"90","author":"Huang","year":"1997","journal-title":"Blood"},{"key":"ref_229","doi-asserted-by":"crossref","first-page":"3454","DOI":"10.1016\/j.febslet.2015.07.027","article-title":"CD73 and CD39 ectonucleotidases in T cell differentiation: Beyond immunosuppression","volume":"589","author":"Bono","year":"2015","journal-title":"FEBS Lett."},{"key":"ref_230","doi-asserted-by":"crossref","unstructured":"Chambers, A.M., Wang, J., Lupo, K.B., Yu, H., Atallah Lanman, N.M., and Matosevic, S. (2018). Adenosinergic Signaling Alters Natural Killer Cell Functional Responses. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.02533"},{"key":"ref_231","doi-asserted-by":"crossref","first-page":"1405","DOI":"10.1007\/s00262-011-1040-4","article-title":"Ectonucleotidases CD39 and CD73 on OvCA cells are potent adenosine-generating enzymes responsible for adenosine receptor 2A-dependent suppression of T cell function and NK cell cytotoxicity","volume":"60","author":"Hausler","year":"2011","journal-title":"Cancer Immunol. Immunother."},{"key":"ref_232","doi-asserted-by":"crossref","unstructured":"Ohta, A., Kini, R., Ohta, A., Subramanian, M., Madasu, M., and Sitkovsky, M. (2012). The development and immunosuppressive functions of CD4+ CD25+ FoxP3+ regulatory T cells are under influence of the adenosine-A2A adenosine receptor pathway. Front. Immunol., 3.","DOI":"10.3389\/fimmu.2012.00190"},{"key":"ref_233","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.canlet.2017.12.032","article-title":"T regulatory cells mediate immunosuppresion by adenosine in peripheral blood, sentinel lymph node and TILs from melanoma patients","volume":"417","author":"Gerlini","year":"2018","journal-title":"Cancer Lett."},{"key":"ref_234","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.coph.2020.07.001","article-title":"Targeting CD73 to augment cancer immunotherapy","volume":"53","author":"Roh","year":"2020","journal-title":"Curr. Opin. Pharmacol."},{"key":"ref_235","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1186\/s12943-023-01733-x","article-title":"CD39\/CD73\/A2AR pathway and cancer immunotherapy","volume":"22","author":"Xia","year":"2023","journal-title":"Mol. Cancer"},{"key":"ref_236","doi-asserted-by":"crossref","unstructured":"Catalan, D., Mansilla, M.A., Ferrier, A., Soto, L., Oleinika, K., Aguillon, J.C., and Aravena, O. (2021). Immunosuppressive Mechanisms of Regulatory B Cells. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.611795"},{"key":"ref_237","doi-asserted-by":"crossref","first-page":"100744","DOI":"10.1016\/j.xcrm.2022.100744","article-title":"Balance between immunoregulatory B cells and plasma cells drives pancreatic tumor immunity","volume":"3","author":"Mirlekar","year":"2022","journal-title":"Cell Rep. Med."},{"key":"ref_238","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1016\/j.annonc.2021.02.009","article-title":"Targeting B cells in pancreatic adenocarcinoma: Does RESOLVE resolve the question?","volume":"32","author":"Philip","year":"2021","journal-title":"Ann. Oncol."},{"key":"ref_239","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1038\/s41586-022-05254-3","article-title":"STING-induced regulatory B cells compromise NK function in cancer immunity","volume":"610","author":"Li","year":"2022","journal-title":"Nature"},{"key":"ref_240","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1111\/imr.12939","article-title":"Regulatory B cells in cancer","volume":"299","author":"Michaud","year":"2021","journal-title":"Immunol. Rev."},{"key":"ref_241","doi-asserted-by":"crossref","unstructured":"Zhu, H., Xu, J., Wang, W., Zhang, B., Liu, J., Liang, C., Hua, J., Meng, Q., Yu, X., and Shi, S. (2024). Intratumoral CD38+ CD19+ B cells associate with poor clinical outcomes and immunosuppression in patients with pancreatic ductal adenocarcinoma. eBioMedicine, 103.","DOI":"10.1016\/j.ebiom.2024.105098"},{"key":"ref_242","doi-asserted-by":"crossref","unstructured":"Geng, X., Chen, H., Zhao, L., Hu, J., Yang, W., Li, G., Cheng, C., Zhao, Z., Zhang, T., and Li, L. (2021). Cancer-Associated Fibroblast (CAF) Heterogeneity and Targeting Therapy of CAFs in Pancreatic Cancer. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.655152"},{"key":"ref_243","doi-asserted-by":"crossref","first-page":"101417","DOI":"10.1016\/j.smim.2020.101417","article-title":"Fibroblast heterogeneity in tumor micro-environment: Role in immunosuppression and new therapies","volume":"48","author":"Mhaidly","year":"2020","journal-title":"Semin. Immunol."},{"key":"ref_244","doi-asserted-by":"crossref","first-page":"5407","DOI":"10.1158\/1078-0432.CCR-18-0125","article-title":"Cancer-Stimulated CAFs Enhance Monocyte Differentiation and Protumoral TAM Activation via IL6 and GM-CSF Secretion","volume":"24","author":"Cho","year":"2018","journal-title":"Clin. Cancer Res."},{"key":"ref_245","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41423-019-0306-1","article-title":"Myeloid immunosuppression and immune checkpoints in the tumor microenvironment","volume":"17","author":"Nakamura","year":"2020","journal-title":"Cell. Mol. Immunol."},{"key":"ref_246","doi-asserted-by":"crossref","first-page":"422","DOI":"10.4049\/jimmunol.1701019","article-title":"Myeloid-Derived Suppressor Cells: Immune-Suppressive Cells That Impair Antitumor Immunity and Are Sculpted by Their Environment","volume":"200","author":"Fenselau","year":"2018","journal-title":"J. Immunol."},{"key":"ref_247","doi-asserted-by":"crossref","first-page":"11795549211035540","DOI":"10.1177\/11795549211035540","article-title":"Targeting MDSC for Immune-Checkpoint Blockade in Cancer Immunotherapy: Current Progress and New Prospects","volume":"15","author":"Li","year":"2021","journal-title":"Clin. Med. Insights Oncol."},{"key":"ref_248","doi-asserted-by":"crossref","first-page":"106939","DOI":"10.1016\/j.intimp.2020.106939","article-title":"Effects of immune cells and cytokines on inflammation and immunosuppression in the tumor microenvironment","volume":"88","author":"Li","year":"2020","journal-title":"Int. Immunopharmacol."},{"key":"ref_249","doi-asserted-by":"crossref","unstructured":"Medvedeva, G.F., Kuzmina, D.O., Nuzhina, J., Shtil, A.A., and Dukhinova, M.S. (2021). How Macrophages Become Transcriptionally Dysregulated: A Hidden Impact of Antitumor Therapy. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22052662"},{"key":"ref_250","doi-asserted-by":"crossref","unstructured":"Pan, Y., Yu, Y., Wang, X., and Zhang, T. (2020). Tumor-Associated Macrophages in Tumor Immunity. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.583084"},{"key":"ref_251","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1016\/j.ccell.2021.04.016","article-title":"The loss of RNA N6-adenosine methyltransferase Mettl14 in tumor-associated macrophages promotes CD8+ T cell dysfunction and tumor growth","volume":"39","author":"Dong","year":"2021","journal-title":"Cancer Cell"},{"key":"ref_252","doi-asserted-by":"crossref","unstructured":"Seifert, A.M., Eymer, A., Heiduk, M., Wehner, R., Tunger, A., von Renesse, J., Decker, R., Aust, D.E., Welsch, T., and Reissfelder, C. (2020). PD-1 Expression by Lymph Node and Intratumoral Regulatory T Cells Is Associated with Lymph Node Metastasis in Pancreatic Cancer. Cancers, 12.","DOI":"10.3390\/cancers12102756"},{"key":"ref_253","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1080\/14728222.2018.1451514","article-title":"FOXP3+ Treg as a therapeutic target for promoting anti-tumor immunity","volume":"22","author":"Whiteside","year":"2018","journal-title":"Expert. Opin. Ther. Targets"},{"key":"ref_254","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1016\/j.trecan.2019.10.013","article-title":"Unmasking the Many Faces of Tumor-Associated Neutrophils and Macrophages: Considerations for Targeting Innate Immune Cells in Cancer","volume":"5","author":"Keeley","year":"2019","journal-title":"Trends Cancer"},{"key":"ref_255","doi-asserted-by":"crossref","unstructured":"Hu, F., Lou, N., Jiao, J., Guo, F., Xiang, H., and Shang, D. (2020). Macrophages in pancreatitis: Mechanisms and therapeutic potential. Biomed. Pharmacother., 131.","DOI":"10.1016\/j.biopha.2020.110693"},{"key":"ref_256","doi-asserted-by":"crossref","first-page":"S98","DOI":"10.1016\/j.clinre.2015.05.018","article-title":"Pancreatic stellate cells: A dynamic player of the intercellular communication in pancreatic cancer","volume":"39","author":"Masamune","year":"2015","journal-title":"Clin. Res. Hepatol. Gastroenterol."},{"key":"ref_257","doi-asserted-by":"crossref","unstructured":"Wang, X., Sun, B., Wang, Y., Gao, P., Song, J., Chang, W., Xiao, Z., Xi, Y., Li, Z., and An, F. (2024). Research progress of targeted therapy regulating Th17\/Treg balance in bone immune diseases. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1333993"},{"key":"ref_258","doi-asserted-by":"crossref","first-page":"26R","DOI":"10.1203\/PDR.0b013e31819e76c7","article-title":"The Treg\/Th17 cell balance: A new paradigm for autoimmunity","volume":"65","author":"Eisenstein","year":"2009","journal-title":"Pediatr. Res."},{"key":"ref_259","doi-asserted-by":"crossref","first-page":"100870","DOI":"10.1016\/j.mam.2020.100870","article-title":"NK cells and ILCs in tumor immunotherapy","volume":"80","author":"Sivori","year":"2021","journal-title":"Mol. Asp. Med."},{"key":"ref_260","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1186\/s12943-020-01238-x","article-title":"Natural killer cells in cancer biology and therapy","volume":"19","author":"Wu","year":"2020","journal-title":"Mol. Cancer"},{"key":"ref_261","doi-asserted-by":"crossref","unstructured":"Pastor, F. (2016). Aptamers: A New Technological Platform in Cancer Immunotherapy. Pharmaceuticals, 9.","DOI":"10.3390\/ph9040064"},{"key":"ref_262","doi-asserted-by":"crossref","first-page":"1083738","DOI":"10.1155\/2016\/1083738","article-title":"Aptamers: A Feasible Technology in Cancer Immunotherapy","volume":"2016","author":"Soldevilla","year":"2016","journal-title":"J. Immunol. Res."},{"key":"ref_263","doi-asserted-by":"crossref","first-page":"1390","DOI":"10.1039\/C8CS00880A","article-title":"Duplexed aptamers: History, design, theory, and application to biosensing","volume":"48","author":"Munzar","year":"2019","journal-title":"Chem. Soc. Rev."},{"key":"ref_264","doi-asserted-by":"crossref","unstructured":"Halder, A., and Sun, Y. (2019). Biocompatible propulsion for biomedical micro\/nano robotics. Biosens. Bioelectron., 139.","DOI":"10.1016\/j.bios.2019.111334"},{"key":"ref_265","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.bios.2019.01.015","article-title":"Aptasensors as a new sensing technology developed for the detection of MUC1 mucin: A review","volume":"130","author":"Yousefi","year":"2019","journal-title":"Biosens. Bioelectron."},{"key":"ref_266","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1186\/s13014-020-01624-1","article-title":"Aptamers: A novel targeted theranostic platform for pancreatic ductal adenocarcinoma","volume":"15","author":"Li","year":"2020","journal-title":"Radiat. Oncol."},{"key":"ref_267","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.addr.2018.08.005","article-title":"Aptamer-based targeted therapy","volume":"134","author":"Zhu","year":"2018","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_268","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1016\/j.ijrobp.2016.05.013","article-title":"4-1BB Aptamer-Based Immunomodulation Enhances the Therapeutic Index of Radiation Therapy in Murine Tumor Models","volume":"96","author":"Benaduce","year":"2016","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_269","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1016\/j.omtn.2017.08.006","article-title":"A CTLA-4 Antagonizing DNA Aptamer with Antitumor Effect","volume":"8","author":"Huang","year":"2017","journal-title":"Mol. Ther.\u2014Nucleic Acids"},{"key":"ref_270","doi-asserted-by":"crossref","unstructured":"Soldevilla, M.M., Hervas, S., Villanueva, H., Lozano, T., Rabal, O., Oyarzabal, J., Lasarte, J.J., Bendandi, M., Inoges, S., and L\u00f3pez-D\u00edaz de Cerio, A. (2017). Identification of LAG3 high affinity aptamers by HT-SELEX and Conserved Motif Accumulation (CMA). PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0185169"},{"key":"ref_271","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1126\/science.aaa4971","article-title":"Neoantigens in cancer immunotherapy","volume":"348","author":"Schumacher","year":"2015","journal-title":"Science"},{"key":"ref_272","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1038\/nrclinonc.2017.88","article-title":"Monitoring immune-checkpoint blockade: Response evaluation and biomarker development","volume":"14","author":"Nishino","year":"2017","journal-title":"Nat. Rev.\u2014Clin. Oncol."},{"key":"ref_273","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1038\/nri.2016.107","article-title":"Immunogenic cell death in cancer and infectious disease","volume":"17","author":"Galluzzi","year":"2017","journal-title":"Nat. Rev. Immunol."},{"key":"ref_274","first-page":"514","article-title":"Cancer Immunotherapy, Part 3: Challenges and Future Trends","volume":"42","author":"Ventola","year":"2017","journal-title":"P T\u2014A Peer-Rev. J. Formul. Manag."},{"key":"ref_275","first-page":"452","article-title":"Cancer Immunotherapy, Part 2: Efficacy, Safety, and Other Clinical Considerations","volume":"42","author":"Ventola","year":"2017","journal-title":"P T"},{"key":"ref_276","doi-asserted-by":"crossref","first-page":"e88328","DOI":"10.1172\/jci.insight.88328","article-title":"Lack of immunoediting in murine pancreatic cancer reversed with neoantigen","volume":"1","author":"Evans","year":"2016","journal-title":"JCI Insight"},{"key":"ref_277","doi-asserted-by":"crossref","first-page":"282","DOI":"10.5306\/wjco.v12.i4.282","article-title":"Tongue swelling as a manifestation of tongue metastasis from pulmonary sarcomatoid carcinoma: A case report","volume":"12","author":"Guo","year":"2021","journal-title":"World J. Clin. Oncol."},{"key":"ref_278","doi-asserted-by":"crossref","first-page":"2056","DOI":"10.1053\/j.gastro.2018.12.038","article-title":"Broadening the Impact of Immunotherapy to Pancreatic Cancer: Challenges and Opportunities","volume":"156","author":"Balachandran","year":"2019","journal-title":"Gastroenterology"}],"container-title":["Medicina"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1648-9144\/61\/10\/1776\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T10:16:20Z","timestamp":1759313780000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1648-9144\/61\/10\/1776"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,1]]},"references-count":278,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2025,10]]}},"alternative-id":["medicina61101776"],"URL":"https:\/\/doi.org\/10.3390\/medicina61101776","relation":{},"ISSN":["1648-9144"],"issn-type":[{"value":"1648-9144","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,1]]}}}