{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T07:17:18Z","timestamp":1771485438845,"version":"3.50.1"},"reference-count":55,"publisher":"Spandidos Publications","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Oncol Lett"],"DOI":"10.3892\/ol.2025.15211","type":"journal-article","created":{"date-parts":[[2025,7,29]],"date-time":"2025-07-29T12:16:58Z","timestamp":1753791418000},"page":"1-12","source":"Crossref","is-referenced-by-count":1,"title":["Immune infiltration and stromal heterogeneity in pancreatic cancer: A prognostic model guiding immunotherapy response"],"prefix":"10.3892","volume":"30","author":[{"given":"Zhilong","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Basic Medicine Science, North Henan Medical University, Xinxiang, Henan 453003, P.R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinlong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Basic Medicine Science, North Henan Medical University, Xinxiang, Henan 453003, P.R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiayi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Basic Medicine Science, North Henan Medical University, Xinxiang, Henan 453003, P.R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fuyong","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Basic Medicine Science, North Henan Medical University, Xinxiang, Henan 453003, P.R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bao","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Basic Medicine Science, North Henan Medical University, Xinxiang, Henan 453003, P.R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanlin","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Basic Medicine Science, North Henan Medical University, Xinxiang, Henan 453003, P.R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaomeng","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Basic Medicine Science, North Henan Medical University, Xinxiang, Henan 453003, P.R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rui","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Respiratory Intervention, Affiliated Cancer Institute of Zhengzhou University, Zhengzhou, Henan 450008, P.R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinwen","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Basic Medicine Science, North Henan Medical University, Xinxiang, Henan 453003, P.R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hao","family":"Wu","sequence":"additional","affiliation":[{"name":"Shenzhen Key Laboratory for Systems Medicine in Inflammatory Diseases, School of Medicine, Shenzhen Campus of Sun Yat\u2011Sen University, Sun Yat\u2011Sen University, Shenzhen, Guangdong 518107, P.R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yongsheng","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Basic Medicine Science, North Henan Medical University, Xinxiang, Henan 453003, P.R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuejiao","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Basic Medicine Science, North Henan Medical University, Xinxiang, Henan 453003, P.R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"2249","published-online":{"date-parts":[[2025,7,29]]},"reference":[{"key":"key20250902113545_b1-ol-30-4-15211","doi-asserted-by":"publisher","first-page":"851","DOI":"10.1001\/jama.2021.13027","article-title":"Pancreatic cancer: A review","volume":"326","author":"Park","year":"2021","journal-title":"JAMA"},{"key":"key20250902113545_b2-ol-30-4-15211","doi-asserted-by":"publisher","first-page":"1729","DOI":"10.1016\/j.cell.2023.02.014","article-title":"Pancreatic cancer: Advances and challenges","volume":"186","author":"Halbrook","year":"2023","journal-title":"Cell"},{"key":"key20250902113545_b3-ol-30-4-15211","doi-asserted-by":"publisher","first-page":"386","DOI":"10.1053\/j.gastro.2022.03.056","article-title":"Pancreatic cancer: Pathogenesis, screening, diagnosis, and treatment","volume":"163","author":"Wood","year":"2022","journal-title":"Gastroenterology"},{"key":"key20250902113545_b4-ol-30-4-15211","doi-asserted-by":"publisher","first-page":"607","DOI":"10.1016\/S0140-6736(10)62307-0","article-title":"Pancreatic cancer","volume":"378","author":"Vincent","year":"2011","journal-title":"Lancet"},{"key":"key20250902113545_b5-ol-30-4-15211","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1186\/s12943-021-01310-0","article-title":"Identification of tumor antigens and immune subtypes of pancreatic adenocarcinoma for mRNA vaccine development","volume":"20","author":"Huang","year":"2021","journal-title":"Mol Cancer"},{"key":"key20250902113545_b6-ol-30-4-15211","doi-asserted-by":"publisher","first-page":"3","DOI":"10.2174\/1389450120666190923162203","article-title":"Bioinformatics approaches for anti-cancer drug discovery","volume":"21","author":"Li","year":"2020","journal-title":"Curr Drug Targets"},{"key":"key20250902113545_b7-ol-30-4-15211","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1016\/j.stem.2023.11.011","article-title":"A pancreatic cancer organoid platform identifies an inhibitor specific to mutant KRAS","volume":"31","author":"Duan","year":"2024","journal-title":"Cell Stem Cell"},{"key":"key20250902113545_b8-ol-30-4-15211","doi-asserted-by":"publisher","first-page":"2155","DOI":"10.3390\/cells11142155","article-title":"Effects of TP53 mutations and mirs on immune responses in the tumor microenvironment important in pancreatic cancer progression","volume":"11","author":"Mccubrey","year":"2022","journal-title":"Cells"},{"key":"key20250902113545_b9-ol-30-4-15211","doi-asserted-by":"publisher","first-page":"418","DOI":"10.1016\/j.ccr.2012.01.007","article-title":"Enzymatic targeting of the stroma ablates physical barriers to treatment of pancreatic ductal adenocarcinoma","volume":"21","author":"Provenzano","year":"2012","journal-title":"Cancer Cell"},{"key":"key20250902113545_b10-ol-30-4-15211","doi-asserted-by":"publisher","first-page":"3296","DOI":"10.1200\/JCO.2003.02.098","article-title":"Comparison of gemcitabine versus the matrix metalloproteinase inhibitor BAY 12-9566 in patients with advanced or metastatic adenocarcinoma of the pancreas: A phase III trial of the national cancer institute of canada clinical trials group","volume":"21","author":"Moore","year":"2003","journal-title":"J Clin Oncol"},{"key":"key20250902113545_b11-ol-30-4-15211","doi-asserted-by":"publisher","first-page":"3447","DOI":"10.1200\/JCO.2001.19.15.3447","article-title":"Marimastat as first-line therapy for patients with unresectable pancreatic cancer: A randomized trial","volume":"19","author":"Bramhall","year":"2001","journal-title":"J Clin Oncol"},{"key":"key20250902113545_b12-ol-30-4-15211","doi-asserted-by":"publisher","first-page":"3052","DOI":"10.1158\/1535-7163.MCT-10-0470","article-title":"Enzymatic depletion of tumor hyaluronan induces antitumor responses in preclinical animal models","volume":"9","author":"Thompson","year":"2010","journal-title":"Mol Cancer Ther"},{"key":"key20250902113545_b13-ol-30-4-15211","doi-asserted-by":"publisher","first-page":"13036","DOI":"10.1073\/pnas.95.22.13036","article-title":"Pancreas development is promoted by cyclopamine, a hedgehog signaling inhibitor","volume":"95","author":"Kim","year":"1998","journal-title":"Proc Natl Acad Sci USA"},{"key":"key20250902113545_b14-ol-30-4-15211","doi-asserted-by":"publisher","first-page":"4284","DOI":"10.1200\/JCO.2015.62.8719","article-title":"Randomized phase Ib\/II study of gemcitabine plus placebo or vismodegib, a hedgehog pathway inhibitor, in patients with metastatic pancreatic cancer","volume":"33","author":"Catenacci","year":"2015","journal-title":"J Clin Oncol"},{"key":"key20250902113545_b15-ol-30-4-15211","doi-asserted-by":"publisher","first-page":"e0211117","DOI":"10.1371\/journal.pone.0211117","article-title":"Blockade of fibroblast activation protein in combination with radiation treatment in murine models of pancreatic adenocarcinoma","volume":"14","author":"Gunderson","year":"2019","journal-title":"PLoS One"},{"key":"key20250902113545_b16-ol-30-4-15211","doi-asserted-by":"publisher","first-page":"1102","DOI":"10.1158\/2159-8290.CD-19-0094","article-title":"Cross-species single-cell analysis of pancreatic ductal adenocarcinoma reveals antigen-presenting cancer-associated fibroblasts","volume":"9","author":"Elyada","year":"2019","journal-title":"Cancer Discov"},{"key":"key20250902113545_b17-ol-30-4-15211","doi-asserted-by":"publisher","first-page":"3561","DOI":"10.1158\/1078-0432.CCR-14-1051","article-title":"Desmoplasia in primary tumors and metastatic lesions of pancreatic cancer","volume":"21","author":"Whatcott","year":"2015","journal-title":"Clin Cancer Res"},{"key":"key20250902113545_b18-ol-30-4-15211","doi-asserted-by":"publisher","first-page":"160","DOI":"10.1016\/j.cell.2019.05.012","article-title":"Stromal microenvironment shapes the intratumoral architecture of pancreatic cancer","volume":"178","author":"Ligorio","year":"2019","journal-title":"Cell"},{"key":"key20250902113545_b19-ol-30-4-15211","doi-asserted-by":"publisher","first-page":"527","DOI":"10.1038\/s41571-020-0363-5","article-title":"The tumour microenvironment in pancreatic cancer-clinical challenges and opportunities","volume":"17","author":"Ho","year":"2020","journal-title":"Nat Rev Clin Oncol"},{"key":"key20250902113545_b20-ol-30-4-15211","doi-asserted-by":"publisher","first-page":"886","DOI":"10.1158\/2326-6066.CIR-18-0822","article-title":"Programmed cell death ligand-1 (PD-L1) and CD8 expression profiling identify an immunologic subtype of pancreatic ductal adenocarcinomas with favorable survival","volume":"7","author":"Danilova","year":"2019","journal-title":"Cancer Immunol Res"},{"key":"key20250902113545_b21-ol-30-4-15211","doi-asserted-by":"publisher","first-page":"1252","DOI":"10.1053\/j.gastro.2013.01.068","article-title":"The epidemiology of pancreatitis and pancreatic cancer","volume":"144","author":"Yadav","year":"2013","journal-title":"Gastroenterology"},{"key":"key20250902113545_b22-ol-30-4-15211","first-page":"2984","article-title":"CD4+ T-cell immunity to mutated ras protein in pancreatic and colon cancer patients","volume":"55","author":"Qin","year":"1995","journal-title":"Cancer Res"},{"key":"key20250902113545_b23-ol-30-4-15211","doi-asserted-by":"publisher","first-page":"e26662","DOI":"10.4161\/onci.26662","article-title":"Vaccine therapy for pancreatic cancer","volume":"2","author":"Salman","year":"2013","journal-title":"Oncoimmunology"},{"key":"key20250902113545_b24-ol-30-4-15211","doi-asserted-by":"publisher","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":"key20250902113545_b25-ol-30-4-15211","doi-asserted-by":"publisher","first-page":"3439","DOI":"10.1158\/0008-5472.CAN-11-3912","article-title":"Regulatory T-cell modulation using cyclophosphamide in vaccine approaches: A current perspective","volume":"72","author":"Le","year":"2012","journal-title":"Cancer Res"},{"key":"key20250902113545_b26-ol-30-4-15211","doi-asserted-by":"publisher","first-page":"846","DOI":"10.1016\/j.ccr.2014.05.016","article-title":"Targeting tumor-associated macrophages with anti-CSF-1R antibody reveals a strategy for cancer therapy","volume":"25","author":"Ries","year":"2014","journal-title":"Cancer Cell"},{"key":"key20250902113545_b27-ol-30-4-15211","doi-asserted-by":"publisher","first-page":"1612","DOI":"10.1126\/science.1198443","article-title":"CD40 agonists alter tumor stroma and show efficacy against pancreatic carcinoma in mice and humans","volume":"331","author":"Beatty","year":"2011","journal-title":"Science"},{"key":"key20250902113545_b28-ol-30-4-15211","doi-asserted-by":"publisher","first-page":"283ra52","DOI":"10.1126\/scitranslmed.aaa4306","article-title":"STING agonist formulated cancer vaccines can cure established tumors resistant to PD-1 blockade","volume":"7","author":"Fu","year":"2015","journal-title":"Sci Transl Med"},{"key":"key20250902113545_b29-ol-30-4-15211","doi-asserted-by":"publisher","first-page":"e000544","DOI":"10.1136\/esmoopen-2019-000544","article-title":"The rationale behind targeting the ICOS-ICOS ligand costimulatory pathway in cancer immunotherapy","volume":"5","author":"Solinas","year":"2020","journal-title":"ESMO Open"},{"key":"key20250902113545_b30-ol-30-4-15211","doi-asserted-by":"publisher","first-page":"800","DOI":"10.1007\/s10637-019-00830-3","article-title":"Phase 1b study of a small molecule antagonist of human chemokine (C-C motif) receptor 2 (PF-04136309) in combination with nab-paclitaxel\/gemcitabine in first-line treatment of metastatic pancreatic ductal adenocarcinoma","volume":"38","author":"Noel","year":"2020","journal-title":"Invest New Drugs"},{"key":"key20250902113545_b31-ol-30-4-15211","doi-asserted-by":"publisher","first-page":"832","DOI":"10.1016\/j.ccell.2016.04.014","article-title":"CXCR2 inhibition profoundly suppresses metastases and augments immunotherapy in pancreatic ductal adenocarcinoma","volume":"29","author":"Steele","year":"2016","journal-title":"Cancer Cell"},{"key":"key20250902113545_b32-ol-30-4-15211","doi-asserted-by":"publisher","first-page":"5846","DOI":"10.1158\/1078-0432.CCR-17-0285","article-title":"Shaping the tumor stroma and sparking immune activation by CD40 and 4-1BB signaling induced by an armed oncolytic virus","volume":"23","author":"Eriksson","year":"2017","journal-title":"Clin Cancer Res"},{"key":"key20250902113545_b33-ol-30-4-15211","doi-asserted-by":"publisher","first-page":"e728","DOI":"10.1038\/cddis.2013.259","article-title":"Reolysin is a novel reovirus-based agent that induces endoplasmic reticular stress-mediated apoptosis in pancreatic cancer","volume":"4","author":"Carew","year":"2013","journal-title":"Cell Death Dis"},{"key":"key20250902113545_b34-ol-30-4-15211","doi-asserted-by":"publisher","first-page":"1561","DOI":"10.1158\/2326-6066.CIR-18-0070","article-title":"Entinostat converts immune-resistant breast and pancreatic cancers into checkpoint-responsive tumors by reprogramming tumor-infiltrating MDSCs","volume":"6","author":"Christmas","year":"2018","journal-title":"Cancer Immunol Res"},{"key":"key20250902113545_b35-ol-30-4-15211","doi-asserted-by":"publisher","first-page":"1035276","DOI":"10.3389\/fimmu.2022.1035276","article-title":"Current landscape and future directions of bispecific antibodies in cancer immunotherapy","volume":"13","author":"Wei","year":"2022","journal-title":"Front Immunol"},{"key":"key20250902113545_b36-ol-30-4-15211","doi-asserted-by":"publisher","first-page":"454","DOI":"10.3390\/molecules29020454","article-title":"Anti-PD-L1-based bispecific antibodies targeting co-inhibitory and co-stimulatory molecules for cancer immunotherapy","volume":"29","author":"Geng","year":"2024","journal-title":"Molecules"},{"key":"key20250902113545_b37-ol-30-4-15211","doi-asserted-by":"publisher","first-page":"5254","DOI":"10.1158\/1078-0432.CCR-22-0308","article-title":"Defactinib, pembrolizumab, and gemcitabine in patients with advanced treatment refractory pancreatic cancer: A phase I dose escalation and expansion study","volume":"28","author":"Wang-Gillam","year":"2022","journal-title":"Clin Cancer Res"},{"key":"key20250902113545_b38-ol-30-4-15211","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1111\/imr.12528","article-title":"The ectonucleotidases CD39 and CD73: Novel checkpoint inhibitor targets","volume":"276","author":"Allard","year":"2017","journal-title":"Immunol Rev"},{"key":"key20250902113545_b39-ol-30-4-15211","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1016\/j.cell.2014.12.018","article-title":"Extracellular metabolic energetics can promote cancer progression","volume":"160","author":"Loo","year":"2015","journal-title":"Cell"},{"key":"key20250902113545_b40-ol-30-4-15211","doi-asserted-by":"publisher","first-page":"a022301","DOI":"10.1101\/cshperspect.a022301","article-title":"Targeting TGF-\u03b2 signaling for therapeutic gain","volume":"9","author":"Akhurst","year":"2017","journal-title":"Cold Spring Harb Perspect Biol"},{"key":"key20250902113545_b41-ol-30-4-15211","doi-asserted-by":"publisher","first-page":"1208","DOI":"10.1038\/s41416-018-0246-z","article-title":"Galunisertib plus gemcitabine vs. gemcitabine for first-line treatment of patients with unresectable pancreatic cancer","volume":"119","author":"Melisi","year":"2018","journal-title":"Br J Cancer"},{"key":"key20250902113545_b42-ol-30-4-15211","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1172\/JCI127515","article-title":"Targeting tumor-intrinsic hexosamine biosynthesis sensitizes pancreatic cancer to anti-PD1 therapy","volume":"130","author":"Sharma","year":"2020","journal-title":"J Clin Invest"},{"key":"key20250902113545_b43-ol-30-4-15211","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1097\/MPA.0b013e3181c15963","article-title":"Phenotype and genotype of pancreatic cancer cell lines","volume":"39","author":"Deer","year":"2010","journal-title":"Pancreas"},{"key":"key20250902113545_b44-ol-30-4-15211","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(\u2212Delta Delta C(T)) method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"key20250902113545_b45-ol-30-4-15211","doi-asserted-by":"publisher","first-page":"5577","DOI":"10.1016\/j.cell.2021.09.022","article-title":"Spatially confined sub-tumor microenvironments in pancreatic cancer","volume":"184","author":"Gr\u00fcnwald","year":"2021","journal-title":"Cell"},{"key":"key20250902113545_b46-ol-30-4-15211","doi-asserted-by":"publisher","first-page":"1511","DOI":"10.1007\/s10147-023-02396-w","article-title":"Impact of Smad4 and p53 mutations on the prognosis of patients with pancreatic ductal adenocarcinoma undergoing chemotherapy","volume":"28","author":"Kamata","year":"2023","journal-title":"Int J Clin Oncol"},{"key":"key20250902113545_b47-ol-30-4-15211","doi-asserted-by":"publisher","first-page":"438","DOI":"10.21147\/j.issn.1000-9604.2023.05.03","article-title":"Epidemiology of pancreatic cancer: New version, new vision","volume":"35","author":"Luo","year":"2023","journal-title":"Chin J Cancer Res"},{"key":"key20250902113545_b48-ol-30-4-15211","doi-asserted-by":"publisher","first-page":"1287459","DOI":"10.3389\/fimmu.2024.1287459","article-title":"Pancreatic cancer tumor microenvironment is a major therapeutic barrier and target","volume":"15","author":"Hartupee","year":"2024","journal-title":"Front Immunol"},{"key":"key20250902113545_b49-ol-30-4-15211","doi-asserted-by":"publisher","first-page":"2129884","DOI":"10.1080\/08941939.2022.2129884","article-title":"Pancreatic cancer: A review of current treatment and novel therapies","volume":"36","author":"Kolbeinsson","year":"2023","journal-title":"J Invest Surg"},{"key":"key20250902113545_b50-ol-30-4-15211","doi-asserted-by":"publisher","first-page":"4298","DOI":"10.3748\/wjg.v27.i27.4298","article-title":"Pancreatic cancer: A review of epidemiology, trend, and risk factors","volume":"27","author":"Hu","year":"2021","journal-title":"World J Gastroenterol"},{"key":"key20250902113545_b51-ol-30-4-15211","doi-asserted-by":"publisher","first-page":"291","DOI":"10.2147\/ITT.S507522","article-title":"Tumor immunotherapy targeting B7-H3: From mechanisms to clinical applications","volume":"14","author":"Guo","year":"2025","journal-title":"Immunotargets Ther"},{"key":"key20250902113545_b52-ol-30-4-15211","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1016\/j.ccc.2010.04.004","article-title":"Immunosupression and infection after major surgery: A nutritional deficiency","volume":"26","author":"Zhu","year":"2010","journal-title":"Crit Care Clin"},{"key":"key20250902113545_b53-ol-30-4-15211","doi-asserted-by":"publisher","first-page":"e2023739118","DOI":"10.1073\/pnas.2023739118","article-title":"Treg-expressed CTLA-4 depletes CD80\/CD86 by trogocytosis, releasing free PD-L1 on antigen-presenting cells","volume":"118","author":"Tekguc","year":"2021","journal-title":"Proc Natl Acad Sci USA"},{"key":"key20250902113545_b54-ol-30-4-15211","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1007\/s13770-022-00430-y","article-title":"Nanozyme-based enhanced cancer immunotherapy","volume":"19","author":"Phan","year":"2022","journal-title":"Tissue Eng Regen Med"},{"key":"key20250902113545_b55-ol-30-4-15211","doi-asserted-by":"publisher","first-page":"532","DOI":"10.1016\/j.annonc.2019.12.008","article-title":"Intratumoral delivery of tavokinogene telseplasmid yields systemic immune responses in metastatic melanoma patients","volume":"31","author":"Algazi","year":"2020","journal-title":"Ann Oncol"}],"container-title":["Oncology Letters"],"original-title":[],"deposited":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T08:35:52Z","timestamp":1756802152000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.spandidos-publications.com\/10.3892\/ol.2025.15211"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,29]]},"references-count":55,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2025,7,29]]}},"URL":"https:\/\/doi.org\/10.3892\/ol.2025.15211","relation":{},"ISSN":["1792-1074","1792-1082"],"issn-type":[{"value":"1792-1074","type":"print"},{"value":"1792-1082","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,29]]}}}