{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T14:15:07Z","timestamp":1785420907516,"version":"3.56.0"},"reference-count":68,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T00:00:00Z","timestamp":1777334400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia","doi-asserted-by":"publisher","award":["SFRH\/BD\/144965\/2019"],"award-info":[{"award-number":["SFRH\/BD\/144965\/2019"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia","doi-asserted-by":"publisher","award":["COVID\/BD\/153545\/2024"],"award-info":[{"award-number":["COVID\/BD\/153545\/2024"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"award":["SFRH\/BD\/144965\/2019"],"award-info":[{"award-number":["SFRH\/BD\/144965\/2019"]}],"id":[{"id":"https:\/\/ror.org\/00snfqn58","id-type":"ROR","asserted-by":"publisher"}]},{"award":["COVID\/BD\/153545\/2024"],"award-info":[{"award-number":["COVID\/BD\/153545\/2024"]}],"id":[{"id":"https:\/\/ror.org\/00snfqn58","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Pancreatic ductal adenocarcinoma (PDAC) has high mortality rates, poor prognosis, and currently limited effective treatments. Natural killer (NK) cells from tumor-infiltrating lymphocytes (TIL) show promise for cancer treatment due to their ability to migrate to the tumor microenvironment (TME) and safe profile. However, expanding functional patient-derived NK cells remains challenging. Here, we cultured, expanded, and characterized TIL-NK cells isolated from central and peripheral tumor regions from PDAC. Ex vivo patient-derived PBMCs and TIL were cultured under IL-2, IL-15, and IL-12 stimulation. Phenotypical and functional NK cell characterization was assessed at the time of surgery and after 12 days of culture evaluating immunophenotype, expansion rate, and activation. A distinct distribution of NK cell infiltration was observed within the TME, with higher NK cell numbers in the periphery of the tumor compared to the central area. Most NK cells displayed a cytotoxic phenotype (CD56+ CD16+). Compared to PBMCs, TIL-NK cells expressed lower activation markers but superior tumor infiltration and expansion rates, particularly those isolated from the central regions. Notably, cytokine stimulation improved patient-derived NK cell activation and cytotoxic profile. This pilot study provides preliminary but critical insights regarding TIL-NK cells from PDAC patients, laying groundwork for developing NK cell-based immunotherapies for solid tumors.<\/jats:p>","DOI":"10.3390\/cells15090797","type":"journal-article","created":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T13:32:22Z","timestamp":1777469542000},"page":"797","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Tumor-Infiltrating Natural Killer Cell Characterization in Pancreatic Ductal Adenocarcinoma"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7860-6219","authenticated-orcid":false,"given":"Andreia","family":"Maia","sequence":"first","affiliation":[{"name":"Molecular and Experimental Pathology Laboratory, Champalimaud Centre for the Unknown, Champalimaud Foundation, 1400-038 Lisbon, Portugal"},{"name":"ImmunoSurgery\/ImmunoTherapy Laboratory, Champalimaud Centre for the Unknown, Champalimaud Foundation, 1400-038 Lisbon, Portugal"},{"name":"NOVA Medical School, NOVA University of Lisbon, 1099-085 Lisbon, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4021-544X","authenticated-orcid":false,"given":"Hasti","family":"Cal\u00e1","sequence":"additional","affiliation":[{"name":"Molecular and Experimental Pathology Laboratory, Champalimaud Centre for the Unknown, Champalimaud Foundation, 1400-038 Lisbon, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6582-7365","authenticated-orcid":false,"given":"Eric","family":"de Sousa","sequence":"additional","affiliation":[{"name":"ImmunoSurgery\/ImmunoTherapy Laboratory, Champalimaud Centre for the Unknown, Champalimaud Foundation, 1400-038 Lisbon, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9874-5259","authenticated-orcid":false,"given":"Joana R.","family":"L\u00e9rias","sequence":"additional","affiliation":[{"name":"ImmunoSurgery\/ImmunoTherapy Laboratory, Champalimaud Centre for the Unknown, Champalimaud Foundation, 1400-038 Lisbon, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina M.","family":"Gorgulho","sequence":"additional","affiliation":[{"name":"ImmunoSurgery\/ImmunoTherapy Laboratory, Champalimaud Centre for the Unknown, Champalimaud Foundation, 1400-038 Lisbon, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-4053-9646","authenticated-orcid":false,"given":"Patr\u00edcia A.","family":"Ant\u00f3nio","sequence":"additional","affiliation":[{"name":"ImmunoSurgery\/ImmunoTherapy Laboratory, Champalimaud Centre for the Unknown, Champalimaud Foundation, 1400-038 Lisbon, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-3900-0934","authenticated-orcid":false,"given":"J\u00e9ssica","family":"Kamiki","sequence":"additional","affiliation":[{"name":"ImmunoSurgery\/ImmunoTherapy Laboratory, Champalimaud Centre for the Unknown, Champalimaud Foundation, 1400-038 Lisbon, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D\u00e1rio","family":"Ligeiro","sequence":"additional","affiliation":[{"name":"ImmunoSurgery\/ImmunoTherapy Laboratory, Champalimaud Centre for the Unknown, Champalimaud Foundation, 1400-038 Lisbon, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4708-438X","authenticated-orcid":false,"given":"Luis M.","family":"Borrego","sequence":"additional","affiliation":[{"name":"Comprehensive Health Research Centre (CHCR), NOVA Medical School, NOVA University of Lisbon, 1099-085 Lisbon, Portugal"},{"name":"Immunoallergy Department, Hospital da Luz, 1600-209 Lisbon, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Maeurer","sequence":"additional","affiliation":[{"name":"ImmunoSurgery\/ImmunoTherapy Laboratory, Champalimaud Centre for the Unknown, Champalimaud Foundation, 1400-038 Lisbon, Portugal"},{"name":"I Medical Clinic, University of Mainz, 55122 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8926-6013","authenticated-orcid":false,"given":"Mireia","family":"Castillo-Martin","sequence":"additional","affiliation":[{"name":"Molecular and Experimental Pathology Laboratory, Champalimaud Centre for the Unknown, Champalimaud Foundation, 1400-038 Lisbon, Portugal"},{"name":"Pathology Service, Champalimaud Clinical Centre, Champalimaud Foundation, 1400-038 Lisbon, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Adamska, A., Domenichini, A., and Falasca, M. (2017). Pancreatic ductal adenocarcinoma: Current and evolving therapies. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18071338"},{"key":"ref_2","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_3","doi-asserted-by":"crossref","unstructured":"Sulciner, M.L., Ashley, S.W., and Molina, G. (2022). Advances and Remaining Challenges in the Treatment for Borderline Resectable and Locally Advanced Pancreatic Ductal Adenocarcinoma. J. Clin. Med., 11.","DOI":"10.3390\/jcm11164866"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Principe, D.R., Underwood, P.W., Korc, M., Trevino, J.G., Munshi, H.G., and Rana, A. (2021). The Current Treatment Paradigm for Pancreatic Ductal Adenocarcinoma and Barriers to Therapeutic Efficacy. Front. Oncol., 11.","DOI":"10.3389\/fonc.2021.688377"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1200\/OP.22.00328","article-title":"Pancreatic Adenocarcinoma Management","volume":"19","author":"Jiang","year":"2023","journal-title":"JCO Oncol. Pract."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1093\/jnci\/86.15.1159","article-title":"Treatment of Patients with Metastatic Melanoma with Autologous Tumor-Infiltrating Lymphocytes and Interleukin 2","volume":"86","author":"Osenberg","year":"1994","journal-title":"J. Natl. Cancer Cent."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"4550","DOI":"10.1158\/1078-0432.CCR-11-0116","article-title":"Durable complete responses in heavily pretreated patients with metastatic melanoma using T-cell transfer immunotherapy","volume":"17","author":"Rosenberg","year":"2011","journal-title":"Clin. Cancer Res."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Wang, S., Sun, J., Chen, K., Ma, P., Lei, Q., Xing, S., Cao, Z., Sun, S., Yu, Z., and Liu, Y. (2021). Perspectives of tumor-infiltrating lymphocyte treatment in solid tumors. BMC Med., 19.","DOI":"10.1186\/s12916-021-02006-4"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1543","DOI":"10.1200\/JCO.2014.58.9093","article-title":"Complete regression of metastatic cervical cancer after treatment with human papillomavirus-targeted tumor-infiltrating T cells","volume":"33","author":"Draper","year":"2015","journal-title":"J. Clin. Oncol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1038\/s41591-018-0040-8","article-title":"Immune recognition of somatic mutations leading to complete durable regression in metastatic breast cancer","volume":"24","author":"Zacharakis","year":"2018","journal-title":"Nat. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1111\/j.1365-2249.2006.03289.x","article-title":"Loss of expression of antigen-presenting molecules in human pancreatic cancer and pancreatic cancer cell lines","volume":"148","author":"Pandha","year":"2007","journal-title":"Clin. Exp. Immunol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.coi.2015.12.007","article-title":"The urgent need to recover MHC class I in cancers for effective immunotherapy","volume":"39","author":"Garrido","year":"2016","journal-title":"Curr. Opin. Immunol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Cornel, A.M., Mimpen, I.L., and Nierkens, S. (2020). MHC class I downregulation in cancer: Underlying mechanisms and potential targets for cancer immunotherapy. Cancers, 12.","DOI":"10.3390\/cancers12071760"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3057","DOI":"10.1111\/cas.14514","article-title":"Expression of classical human leukocyte antigen class I antigens, HLA-E and HLA-G, is adversely prognostic in pancreatic cancer patients","volume":"111","author":"Hiraoka","year":"2020","journal-title":"Cancer Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"19352","DOI":"10.1002\/jcp.28657","article-title":"NK cells: An attractive candidate for cancer therapy","volume":"234","author":"Valipour","year":"2019","journal-title":"J. Cell. Physiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1007\/s12032-019-1307-8","article-title":"Circulating CD16+CD56+ nature killer cells indicate the prognosis of colorectal cancer after initial chemotherapy","volume":"36","author":"Cui","year":"2019","journal-title":"Med. Oncol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1038\/s41388-020-01561-z","article-title":"The role of natural killer cell in gastrointestinal cancer: Killer or helper","volume":"40","author":"Wang","year":"2021","journal-title":"Oncogene"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3805","DOI":"10.4049\/jimmunol.1301889","article-title":"CD56 bright Perforin low Noncytotoxic Human NK Cells Are Abundant in Both Healthy and Neoplastic Solid Tissues and Recirculate to Secondary Lymphoid Organs via Afferent Lymph","volume":"192","author":"Carrega","year":"2014","journal-title":"J. Immunol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1038\/s41590-020-0728-z","article-title":"The NK cell\u2013cancer cycle: Advances and new challenges in NK cell\u2013based immunotherapies","volume":"21","author":"Bald","year":"2020","journal-title":"Nat. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"105","DOI":"10.21037\/atm.2019.01.42","article-title":"NK-mediated antibody-dependent cell-mediated cytotoxicity in solid tumors: Biological evidence and clinical perspectives","volume":"7","author":"Macagno","year":"2019","journal-title":"Ann. Transl. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1186\/s13045-022-01382-5","article-title":"Natural killer cells in clinical development as non-engineered, engineered, and combination therapies","volume":"15","author":"Panella","year":"2022","journal-title":"J. Hematol. Oncol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1186\/s12967-022-03437-0","article-title":"Natural killer cells: A promising immunotherapy for cancer","volume":"20","author":"Chu","year":"2022","journal-title":"J. Transl. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1093\/stcltm\/szad087","article-title":"Genetic Manipulation Approaches to Enhance the Clinical Application of NK Cell-Based Immunotherapy","volume":"13","author":"Maia","year":"2024","journal-title":"Stem Cells Transl. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3321","DOI":"10.1182\/blood-2016-04-703751","article-title":"Toxicities of chimeric antigen receptor T cells: Recognition and management","volume":"127","author":"Brudno","year":"2016","journal-title":"Blood"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1002\/ajh.25445","article-title":"Toxicities of CD19 CAR-T cell immunotherapy","volume":"94","author":"Hirayama","year":"2019","journal-title":"Am. J. Hematol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1038\/s41591-023-02785-8","article-title":"Safety, efficacy and determinants of response of allogeneic CD19-specific CAR-NK cells in CD19+ B cell tumors: A phase 1\/2 trial","volume":"30","author":"Marin","year":"2024","journal-title":"Nat. Med."},{"key":"ref_27","first-page":"30","article-title":"Cytokine-Induced Memory-Like NK Cells for Improved Cancer Immunotherapy","volume":"47","author":"Maia","year":"2023","journal-title":"ASHI Q. Second Quart."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1615\/CritRevOncog.2014010931","article-title":"Clinical Grade Purification and Expansion of Natural Killer Cells","volume":"19","author":"Lapteva","year":"2014","journal-title":"Crit. Rev. Oncog."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1016\/j.trecan.2020.02.022","article-title":"Turning Cold into Hot: Firing up the Tumor Microenvironment","volume":"6","author":"Duan","year":"2020","journal-title":"Trends Cancer"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1038\/nprot.2014.006","article-title":"Full-length RNA-seq from single cells using Smart-seq2","volume":"9","author":"Picelli","year":"2014","journal-title":"Nat. Protoc."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"D891","DOI":"10.1093\/nar\/gkad1049","article-title":"Ensembl 2024","volume":"52","author":"Harrison","year":"2024","journal-title":"Nucleic Acids Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","article-title":"STAR: Ultrafast universal RNA-seq aligner","volume":"29","author":"Dobin","year":"2013","journal-title":"Bioinformatics"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","volume":"15","author":"Love","year":"2014","journal-title":"Genome Biol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1093\/nar\/gkad347","article-title":"g:Profiler-interoperable web service for functional enrichment analysis and gene identifier mapping (2023 update)","volume":"51","author":"Kolberg","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.ejca.2020.03.013","article-title":"The prognostic value of tumour-infiltrating lymphocytes in pancreatic cancer: A systematic review and meta-analysis","volume":"132","author":"Orhan","year":"2020","journal-title":"Eur. J. Cancer"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"100930","DOI":"10.1016\/j.tranon.2020.100930","article-title":"NK cell infiltration is associated with improved overall survival in solid cancers: A systematic review and meta-analysis","volume":"14","author":"Nersesian","year":"2021","journal-title":"Transl. Oncol."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Heipertz, E.L., Zynda, E.R., Stav-Noraas, T.E., Hungler, A.D., Boucher, S.E., Kaur, N., and Vemuri, M.C. (2021). Current Perspectives on \u201cOff-The-Shelf\u201d Allogeneic NK and CAR-NK Cell Therapies. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.732135"},{"key":"ref_38","first-page":"693","article-title":"Pancreatic Ductal Adenocarcinoma: Characteristics of Tumor Microenvironment and Barriers to Treatment","volume":"11","author":"Kane","year":"2020","journal-title":"J. Adv. Pract. Oncol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1845424","DOI":"10.1080\/2162402X.2020.1845424","article-title":"NK cells in pancreatic cancer demonstrate impaired cytotoxicity and a regulatory IL-10 phenotype","volume":"9","author":"Marcon","year":"2020","journal-title":"Oncoimmunology"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Lim, S.A., Kim, J., Jeon, S., Shin, M.H., Kwon, J., Kim, T.J., Im, K., Han, Y., Kwon, W., and Kim, S.W. (2019). Defective localization with impaired tumor cytotoxicity contributes to the immune escape of NK cells in pancreatic cancer patients. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.00496"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Navarro, A.G., Bj\u00f6rklund, A.T., and Chekenya, M. (2015). Therapeutic potential and challenges of natural killer cells in treatment of solid tumors. Front. Immunol., 6.","DOI":"10.3389\/fimmu.2015.00202"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"3599","DOI":"10.1182\/blood-2012-04-425397","article-title":"NK cell CD16 surface expression and function is regulated by a disintegrin and metalloprotease-17 (ADAM17)","volume":"121","author":"Romee","year":"2013","journal-title":"Blood"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Martin-Iglesias, S., Herrera, L., Santos, S., Vesga, M.\u00c1., Eguizabal, C., Lanceros-Mendez, S., and Silvan, U. (2023). Analysis of the impact of handling and culture on the expansion and functionality of NK cells. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1225549"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Yang, Y., and Lundqvist, A. (2020). Immunomodulatory effects of il-2 and il-15; implications for cancer immunotherapy. Cancers, 12.","DOI":"10.3390\/cancers12123586"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"675","DOI":"10.3892\/etm.2021.10107","article-title":"Therapeutic potential of interleukin 15 in cancer","volume":"22","author":"Isvoranu","year":"2021","journal-title":"Exp. Ther. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"4042","DOI":"10.1172\/JCI90387","article-title":"CD56bright NK cells exhibit potent antitumor responses following IL-15 priming","volume":"127","author":"Wagner","year":"2017","journal-title":"J. Clin. Investig."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1038\/ni.2936","article-title":"The metabolic checkpoint kinase mTOR is essential for IL-15 signaling during the development and activation of NK cells","volume":"15","author":"Viant","year":"2014","journal-title":"Nat. Immunol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/j.molimm.2017.06.025","article-title":"IL-18\/IL-15\/IL-12 synergy induces elevated and prolonged IFN-\u03b3 production by ex vivo expanded NK cells which is not due to enhanced STAT4 activation","volume":"88","author":"Lusty","year":"2017","journal-title":"Mol. Immunol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"104811","DOI":"10.1016\/j.ebiom.2023.104811","article-title":"Mapping the chemotactic landscape in NK cells reveals subset-specific synergistic migratory responses to dual chemokine receptor ligation","volume":"96","author":"Lachota","year":"2023","journal-title":"eBioMedicine"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1002\/cncr.23239","article-title":"Natural killer cells infiltrating human nonsmall-cell lung cancer are enriched in CD56brightCD16\u2212 cells and display an impaired capability to kill tumor cells","volume":"112","author":"Carrega","year":"2008","journal-title":"Cancer"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1038\/s41589-021-00918-z","article-title":"Identification and mechanism of G protein-biased ligands for chemokine receptor CCR1","volume":"18","author":"Shao","year":"2022","journal-title":"Nat. Chem. Biol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.omto.2019.12.006","article-title":"CXCR1 Expression to Improve Anti-Cancer Efficacy of Intravenously Injected CAR-NK Cells in Mice with Peritoneal Xenografts","volume":"16","author":"Ng","year":"2020","journal-title":"Mol. Ther. Oncolytics"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"3541","DOI":"10.1038\/s41388-020-1237-0","article-title":"XCL1 expression correlates with CD8-positive T cells infiltration and PD-L1 expression in squamous cell carcinoma arising from mature cystic teratoma of the ovary","volume":"39","author":"Tamura","year":"2020","journal-title":"Oncogene"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Tong, X., Ru, Y., Fu, J., Wang, Y., Zhu, J., Ding, Y., Lv, F., Yang, M., Wei, X., and Liu, C. (2022). Fucosylation Promotes Cytolytic Function and Accumulation of NK Cells in B Cell Lymphoma. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.904693"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.2147\/JIR.S296597","article-title":"Fut7 promotes the epithelial\u2013mesenchymal transition and immune infiltration in bladder urothelial carcinoma","volume":"14","author":"Liu","year":"2021","journal-title":"J. Inflamm. Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1007\/s12307-010-0057-0","article-title":"Matrix metalloproteinases in cytotoxic lymphocytes impact on tumour infiltration and immunomodulation","volume":"4","author":"Edsparr","year":"2011","journal-title":"Cancer Microenviron."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1016\/j.immuni.2019.03.012","article-title":"Interleukin-1 and Related Cytokines in the Regulation of Inflammation and Immunity","volume":"50","author":"Mantovani","year":"2019","journal-title":"Immunity"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1007\/s00005-012-0199-5","article-title":"Function of junctional adhesion molecules (JAMs) in leukocyte migration and homeostasis","volume":"61","author":"Arcangeli","year":"2013","journal-title":"Arch. Immunol. Ther. Exp."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1038\/s41467-024-44789-z","article-title":"Rapid functional impairment of natural killer cells following tumor entry limits anti-tumor immunity","volume":"15","author":"Dean","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Ziblat, A., Nu\u00f1ez, S.Y., Raffo Iraolagoitia, X.L., Spallanzani, R.G., Torres, N.I., Sierra, J.M., Secchiari, F., Domaica, C.I., Fuertes, M.B., and Zwirner, N.W. (2018). Interleukin (IL)-23 stimulates IFN-\u03b3 secretion by CD56bright natural killer cells and enhances IL-18-driven dendritic cells activation. Front. Immunol., 8.","DOI":"10.3389\/fimmu.2017.01959"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Afferni, C., Buccione, C., Andreone, S., Galdiero, M.R., Varricchi, G., Marone, G., Mattei, F., and Schiavoni, G. (2018). The pleiotropic immunomodulatory functions of IL-33 and its implications in tumor immunity. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.02601"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1182\/blood-2016-12-756585","article-title":"CD70 reverse signaling enhances NK cell function and immunosurveillance in CD27-expressing B-cell malignancies","volume":"130","author":"Ruckstuhl","year":"2017","journal-title":"Blood"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1111\/j.1365-2567.2011.03513.x","article-title":"Interleukin-32 enhances cytotoxic effect of natural killer cells to cancer cells via activation of death receptor 3","volume":"135","author":"Park","year":"2012","journal-title":"Immunology"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Peng, Y., Luo, G., Zhou, J., Wang, X., Hu, J., Cui, Y., Li, X.C., Tan, J., Yang, S., and Zhan, R. (2013). CD86 is an activation receptor for nk cell cytotoxicity against tumor cells. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0083913"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Maia, A., Tarannum, M., L\u00e9rias, J.R., Piccinelli, S., Borrego, L.M., Maeurer, M., Romee, R., and Castillo-Martin, M. (2024). Building a Better Defense: Expanding and Improving Natural Killer Cells for Adoptive Cell Therapy. Cells, 13.","DOI":"10.3390\/cells13050451"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"3841","DOI":"10.1038\/s41467-019-11632-9","article-title":"Unique transcriptional and protein-expression signature in human lung tissue-resident NK cells","volume":"10","author":"Marquardt","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Fend, L., Rusakiewicz, S., Adam, J., Bastien, B., Caignard, A., Messaoudene, M., Iribarren, C., Cremer, I., Marabelle, A., and Borg, C. (2017). Prognostic impact of the expression of NCR1 and NCR3 nk cell receptors and PD-L1 on advanced non-small cell lung cancer. Oncoimmunology, 6.","DOI":"10.1080\/2162402X.2016.1163456"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.cytogfr.2014.11.003","article-title":"NK cells and interferons","volume":"26","author":"Paolini","year":"2015","journal-title":"Cytokine Growth Factor Rev."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/9\/797\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T13:42:48Z","timestamp":1777470168000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/9\/797"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,28]]},"references-count":68,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["cells15090797"],"URL":"https:\/\/doi.org\/10.3390\/cells15090797","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,28]]}}}