{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T23:54:54Z","timestamp":1793145294102,"version":"4.5.0"},"reference-count":48,"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                    Colorectal cancer (CRC) develops within a mucosal ecosystem in which epithelial barrier function, colonizing microbes, inflammatory signaling, and immune cell composition are closely interdependent. Immune checkpoint inhibitors have significantly altered treatment outcomes in patients with mismatch repair-deficient or microsatellite instability-high (dMMR\/MSI-H) CRC, but most microsatellite-stable (MSS) tumors still respond poorly, and this is not solely due to lower antigenicity. This article explains this gap mechanistically: gut microbiota dysbiosis weakens the mucosal barrier, promotes microbial translocation, amplifies cytokine and eicosanoid signaling, and remodels the tumor microenvironment into an immunosuppressive state dominated by myeloid cells. We focus on\n                    <jats:italic>Fusobacterium nucleatum<\/jats:italic>\n                    and enterotoxigenic\n                    <jats:italic>Bacteroides fragilis<\/jats:italic>\n                    , microbial metabolites, tight junction disruption, and the IL-6\/STAT3, NF-\u03baB, TNF-alpha, and COX-2\/PGE2 pathways that link epithelial stress with innate immune remodeling. Downstream processes include tumor-associated macrophages, myeloid-derived suppressor cells, neutrophil polarization, dendritic cell dysfunction, regulatory T cells, cancer-associated fibroblasts, CXCL12-mediated T-cell exclusion, and hypoxia. These processes collectively create a spatially structured drug-resistance niche, preventing effector T cells from functioning effectively, rather than simply resulting in an immunologically \u201ccold\u201d tumor. We believe that integrating this microbiota-barrier-myeloid axis into biomarker development and mechanism-matched combination therapy design offers a more rational and promising approach to overcoming immunotherapy resistance in CRC, especially in MSS disease, compared to empirical drug combinations.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1932590","type":"journal-article","created":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T11:25:36Z","timestamp":1787311536000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["From gut microbiota-driven mucosal barrier disruption to myeloid-dominant immunosuppressive niches in colorectal cancer"],"prefix":"10.3389","volume":"17","author":[{"given":"Na","family":"Lu","sequence":"first","affiliation":[{"name":"Research Center of Traditional Chinese Medicine and Clinical Pharmacy, Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University","place":["Jinan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Research Center of Traditional Chinese Medicine and Clinical Pharmacy, Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University","place":["Jinan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanyu","family":"Sun","sequence":"additional","affiliation":[{"name":"School of Public Health, Shenyang Medical College","place":["Shenyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuwenshu","family":"Zhou","sequence":"additional","affiliation":[{"name":"School of Public Health, Shenyang Medical College","place":["Shenyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Panli","family":"He","sequence":"additional","affiliation":[{"name":"School of Public Health, Shenyang Medical College","place":["Shenyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changrui","family":"Zhao","sequence":"additional","affiliation":[{"name":"The First Clinical Medical College, Shenyang Medical College","place":["Shenyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Public Health, Shenyang Medical College","place":["Shenyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,21]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21660","article-title":"Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J 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