{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T11:36:16Z","timestamp":1787312176557,"version":"build-2736575974"},"reference-count":169,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T00:00:00Z","timestamp":1787270400000},"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                    The gut microbiota and natural killer (NK) cells jointly shape colorectal cancer (CRC) progression and immunotherapy response, yet existing reviews largely adopt a linear, pathogen-centric view that overlooks NK-cell heterogeneity and spatial tumor microenvironment architecture. We propose an integrated framework centered on three progressive pillars: (i) the microbiota appears to selectively shape three well-characterized NK-cell states (activated, dysfunctional, and memory-like), with a fourth regulatory-like state that remains mechanistically uncharacterized through metabolically and genetically mediated mechanisms; (ii) emerging spatial evidence suggests beneficial commensals and activated NK cells preferentially localize to perivascular niches, whereas pathogenic bacteria and dysfunctional NK cells are enriched within the tumor parenchyma, though multicenter validation is needed; and (iii) these insights support two testable patient-stratification strategies for future clinical testing, an \u201cenrichment\u201d approach for tumors with pre-existing activated NK signatures, and a \u201cremodeling\u201d approach for Fusobacterium nucleatum (\n                    <jats:italic>F. nucleatum<\/jats:italic>\n                    )-dominant immunosuppressive microenvironments, particularly in refractory microsatellite-stable disease. This framework seeks to shift the field toward a subset-centric, spatially resolved, and clinically testable model of the microbiota-NK axis, designed to generate hypotheses and guide prospective cohort studies rather than replace current standards.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1934819","type":"journal-article","created":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T11:21:52Z","timestamp":1787311312000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["The microbiota-NK cell axis in colorectal cancer: a spatial and subset-centric framework"],"prefix":"10.3389","volume":"17","author":[{"given":"Jiexia","family":"Wen","sequence":"first","affiliation":[{"name":"Department of Central Laboratory, The First Hospital of Qinhuangdao","place":["Qinhuangdao, Hebei, China"]},{"name":"Key Laboratory of Research on Molecular Mechanism of Gastrointestinal Tumors in Qinhuangdao, The First Hospital of Qinhuangdao","place":["Qinhuangdao, Hebei, China"]},{"name":"Joint Laboratory for Tumor Pathogenesis and Precision Medicine, The First Hospital of Qinhuangdao, State Key Laboratory of Neurology and Oncology Drug Development","place":["Qinhuangdao, Hebei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunhuan","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Immunology, Nankai University School of Medicine, Nankai University","place":["Tianjin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meimei","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, The First Hospital of Qinhuangdao","place":["Qinhuangdao, Hebei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muran","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Tianjin Union Medical Center, The First Affiliated Hospital of Nankai 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