{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T19:51:45Z","timestamp":1788292305490,"version":"build-2803163510"},"reference-count":158,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T00:00:00Z","timestamp":1773878400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    Pancreatic ductal adenocarcinoma (PDAC) remains an intractable cancer marked by delayed diagnosis, rapid progression, and significant resistance to current treatments. Conventional biomarkers, such as CA19-9, have insufficient sensitivity and specificity. Meanwhile, the practical use of newer markers such as the tumor mutational burden and microsatellite instability is limited by the absence of standardized testing protocols and definitive threshold values. Circulating tumor DNA and exosomal miRNA hold promise for continuously tracking tumor dynamics and effectiveness of immunotherapy, but additional validation is necessary before their routine clinical application. Recent advancements in multiomics, nanotechnology, and artificial intelligence have opened new possibilities for more accurate and comprehensive biomarkers. For instance, Shah et\u00a0al. developed shortwave-infrared-emitting nanoprobes to specifically target CD8\n                    <jats:sup>+<\/jats:sup>\n                    cytotoxic T cells, permitting high-sensitivity\n                    <jats:italic>in vivo<\/jats:italic>\n                    imaging in breast cancer models. Batool et\u00a0al. utilized nanoplasmonic sensors to detect changes in serum programmed death-ligand 1 and cytokine levels within 1\u20132 weeks post-treatment, achieving picomolar sensitivity. Chang et\u00a0al. combined fluorescence and photoacoustic imaging in the NanoTrackThera platform, facilitating the real-time monitoring of immunotherapy efficacy. This review highlights the evolution of PDAC biomarkers from traditional markers to multimodal integration and dynamic monitoring. The limitations of current markers and potential of emerging technologies, including metabolic reprogramming markers, epigenetic regulators, and AI-driven predictive models, are discussed. Future directions include multicenter prospective trials to validate multimodal models, standardize detection methods, and increase interdisciplinary collaboration. By integrating genomic, epigenetic, metabolic, and microbiome data, these models can better capture the complexity of PDAC, thereby improving patient outcomes through precision immunotherapy.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1686658","type":"journal-article","created":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T07:09:18Z","timestamp":1773904158000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Pancreatic cancer immunotherapy biomarkers: from traditional markers to multimodal integration and dynamic monitoring"],"prefix":"10.3389","volume":"17","author":[{"given":"Wei-Yi","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Hepatopancreatobiliary Surgery of Second Hospital of Jilin University, Jilin University","place":["Changchun, China"]},{"name":"Department of Clinical Pathology of Yanbian Hospital of Yanbian University, Yanbian University","place":["Yanji, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin-Wei","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Hepatopancreatobiliary Surgery of Second Hospital of Jilin University, Jilin University","place":["Changchun, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,19]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","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":"B2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.21.02511","article-title":"Randomized phase II study of nivolumab with or without ipilimumab combined with stereotactic body radiotherapy for refractory metastatic pancreatic cancer (CheckPAC)","volume":"40","author":"Chen","year":"2022","journal-title":"J Clin Oncol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.3389\/fmolb.2023.1051491","article-title":"Companion diagnostic requirements for spatial biology using multiplex immunofluorescence and multispectral imaging","volume":"10","author":"Locke","year":"2023","journal-title":"Front Mol Biosci"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1097\/MPA.0000000000002489","article-title":"Factors driving pancreatic cancer survival rates","volume":"54","author":"Rahib","year":"2025","journal-title":"Pancreas"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1910836","article-title":"Five-year survival with combined nivolumab and ipilimumab in advanced melanoma","volume":"381","author":"Larkin","year":"2019","journal-title":"N Engl J Med"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1801005","article-title":"Pembrolizumab plus chemotherapy in metastatic non-small-cell lung cancer","volume":"378","author":"Gandhi","year":"2018","journal-title":"N Engl J Med"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1712126","article-title":"Nivolumab plus Ipilimumab versus Sunitinib in Advanced Renal-Cell Carcinoma","volume":"378","author":"Motzer","year":"2018","journal-title":"N Engl J Med"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-020-0939-1","article-title":"A phase 1b study of dual PD-1 and CTLA-4 or KIR blockade in patients with relapsed\/refractory lymphoid Malignancies","volume":"35","author":"Armand","year":"2021","journal-title":"Leukemia"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1097\/CJI.0b013e3181eec14c","article-title":"Phase 2 trial of single agent Ipilimumab (anti-CTLA-4) for locally advanced or metastatic pancreatic adenocarcinoma","volume":"33","author":"Royal","year":"2010","journal-title":"J Immunother"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2019.1588","article-title":"Durvalumab with or without tremelimumab for patients with metastatic pancreatic ductal adenocarcinoma: A phase 2 randomized clinical trial","volume":"5","author":"O'Reilly","year":"2019","journal-title":"JAMA Oncol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14102429","article-title":"Immunotherapy in pancreatic cancer: why do we keep failing? 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