{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T23:19:25Z","timestamp":1785799165302,"version":"3.56.0"},"reference-count":104,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T00:00:00Z","timestamp":1781136000000},"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>Immune checkpoint inhibitors (ICIs) have transformed advanced gastric cancer (GC) treatment, but durable responses remain rare, highlighting the need for better patient selection. Recent studies suggest that host-derived autoantibodies (e.g., ANA, ENA) may serve as prognostic markers in GC patients receiving immunotherapy. These hypothesis-generating observations indicate that pre-existing humoral immunity could reflect a clinically relevant axis of immune fitness. This review critically appraises these findings alongside established and emerging predictive biomarkers. We examine the strengths and limitations of PD-L1, MSI, TMB, and EBV status, and explore the clinical potential of dynamic tools like ctDNA and computational models. We also discuss emerging evidence on intrinsic resistance to PD-1 blockade in MSI-H GC, including PTEN mutations, low TMB within MSI-H tumors, and antigen presentation defects. Murine models have provided key insights into these resistance mechanisms and the immunomodulatory role of the gut microbiome. Collectively, the data support a shift from single-analyte biomarkers toward integrative, dynamic, systems-level models for patient selection, heralding a new era of precision immune-oncology in GC. However, most emerging biomarkers remain investigational and require prospective validation.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1847526","type":"journal-article","created":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T05:47:57Z","timestamp":1781156877000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Rethinking biomarker strategy in gastric cancer immunotherapy: from tumor to host"],"prefix":"10.3389","volume":"17","author":[{"given":"Nabil","family":"Ismaili","sequence":"first","affiliation":[{"name":"Department of Medical Oncology, Mohammed VI Faculty of Medicine, Mohammed VI University of Sciences and Health (UM6SS)","place":["Casablanca, Morocco"]},{"name":"Mohammed VI Foundation of Sciences and Health (FM6SS)","place":["Rabat, Morocco"]},{"name":"Oncopathology, Biology and Environment of Cancer Laboratory, Mohammed VI Center of Research and Innovation (CM6RI)","place":["Rabat, 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