{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T23:19:41Z","timestamp":1793056781970,"version":"4.5.0"},"reference-count":84,"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>\n                    Gastric and colorectal cancers are leading causes of global cancer mortality, yet the transformative benefits of immune checkpoint blockade remain largely confined to the small fraction of patients with MSI-H\/dMMR tumors. The vast majority\u2014those with MSS\/pMMR disease\u2014exhibit primary resistance, underscoring an urgent need to look beyond bulk immune infiltration and dissect the\n                    <jats:italic>in situ<\/jats:italic>\n                    spatial determinants of immune evasion. We propose that immunotherapy outcome in these malignancies is dictated not by lymphocyte abundance alone, but by highly coordinated multicellular architectures\u2014termed spatial immune archetypes\u2014that govern immune exclusion, metabolic suppression, local activation, and epithelial-immune contact. Enabled by spatial transcriptomics, multiplexed proteomics, and multimodal computational integration, this review proposes a conceptual framework of four spatial archetypes synthesized from existing evidence across gastric and colorectal cancers: (i) the stromal-excluded barrier niche, characterized by CAF-mediated physical sequestration; (ii) the myeloid-suppressive metabolic niche, driven by TREM2+\/SPP1TREM2+ macrophages and microbial crosstalk; (iii) the inflamed lymphoid-reactive niche, marked by mature tertiary lymphoid structures; and (iv) the epithelial-immune interface niche, a fragile surveillance equilibrium lost during immunoediting. We further examine how tissue-specific anatomical constraints and distinct microbial ecologies (\n                    <jats:italic>H. pylori<\/jats:italic>\n                    in the stomach,\n                    <jats:italic>F. nucleatum<\/jats:italic>\n                    in the colon) shape the prevalence of each archetype. By elucidating the molecular circuits and environmental dependencies underlying these spatially encoded resistance programs, we articulate a translational imperative: archetype-guided spatial biomarkers and targeted microenvironment-remodeling strategies provide the most viable framework to extend durable immunotherapeutic benefit to the historically refractory MSS\/pMMR gastrointestinal cancer population.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1859228","type":"journal-article","created":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T05:47:47Z","timestamp":1781156867000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Spatial immune archetypes in gastric and colorectal cancer: a proposed conceptual framework for immunotherapy resistance and therapeutic remodeling"],"prefix":"10.3389","volume":"17","author":[{"given":"Songlin","family":"Sun","sequence":"first","affiliation":[{"name":"Second Department of Gastrointestinal Surgery, Hepatobiliary, Pancreatic and Intestinal Diseases Research Institute, The Affiliated Hospital of North Sichuan Medical College, National Clinical Key Specialty (General Surgery), Sub-center of National Clinical Research Center for Digestive Diseases, Sichuan Clinical Research Center for Digestive Diseases","place":["Nanchong, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yicong","family":"Zeng","sequence":"additional","affiliation":[{"name":"Second Department of Gastrointestinal Surgery, Hepatobiliary, Pancreatic and Intestinal Diseases Research Institute, The Affiliated Hospital of North Sichuan Medical College, National Clinical Key Specialty (General Surgery), Sub-center of National Clinical Research Center for Digestive Diseases, Sichuan Clinical Research Center for Digestive Diseases","place":["Nanchong, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiahan","family":"Chen","sequence":"additional","affiliation":[{"name":"Second Department of Gastrointestinal Surgery, Hepatobiliary, Pancreatic and Intestinal Diseases Research Institute, The Affiliated Hospital of North Sichuan Medical College, National Clinical Key Specialty (General Surgery), Sub-center of National Clinical Research Center for Digestive Diseases, Sichuan Clinical Research Center for Digestive Diseases","place":["Nanchong, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Zhong","sequence":"additional","affiliation":[{"name":"Second Department of Gastrointestinal Surgery, Hepatobiliary, Pancreatic and Intestinal Diseases Research Institute, The Affiliated Hospital of North Sichuan Medical College, National Clinical Key Specialty (General Surgery), Sub-center of National Clinical Research Center for Digestive Diseases, Sichuan Clinical Research Center for Digestive Diseases","place":["Nanchong, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tong","family":"Zhou","sequence":"additional","affiliation":[{"name":"Second Department of Gastrointestinal Surgery, Hepatobiliary, Pancreatic and Intestinal Diseases Research Institute, The Affiliated Hospital of North Sichuan Medical College, National Clinical Key Specialty (General Surgery), Sub-center of National Clinical Research Center for Digestive Diseases, Sichuan Clinical Research Center for Digestive Diseases","place":["Nanchong, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,11]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14092140","article-title":"Immunomodulation by gut microbiome on gastrointestinal cancers: focusing on colorectal 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