{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T17:47:40Z","timestamp":1793468860450,"version":"4.5.0"},"reference-count":98,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T00:00:00Z","timestamp":1774396800000},"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                    Fusobacterium nucleatum, a key oral-pathobiont in colorectal cancer (CRC), has evolved from a presumed \u201cpassenger\u201d to an active \u201cco-conspirator\u201d in tumorigenesis. This review systematically delineates its core role as an \u201carchitect of the immune microenvironment,\u201d whereby it remodels T-cell immune responses through precise mechanisms to establish an immunosuppressive tumor microenvironment. Specifically,\n                    <jats:italic>F. nucleatum<\/jats:italic>\n                    employs virulence factors such as Fap2 and FadA for specific colonization, and achieves immune evasion by inhibiting NK and T-cell function and recruiting myeloid-derived suppressor cells (MDSCs). Post-colonization, it further fine-tunes T-cell subsets: driving Th17 polarization to create a pro-inflammatory milieu while suppressing the infiltration and function of CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells and promoting their exhaustion. Intriguingly, it upregulates programmed death-ligand 1 (PD-L1) expression, which may conversely enhance tumor sensitivity to anti-PD-1\/PD-L1 immunotherapy. Moreover, it collaborates with other microbes via quorum sensing and the oral-gut axis to construct a procarcinogenic ecosystem. Based on these mechanisms,\n                    <jats:italic>F. nucleatum<\/jats:italic>\n                    exhibits substantial clinical translational potential. Its load serves as an effective non-invasive diagnostic biomarker and a prognostic predictor, and may help predict responses to immune checkpoint inhibitors. Therapeutically, strategies targeting the eradication or inhibition of\n                    <jats:italic>F. nucleatum<\/jats:italic>\n                    \u2014including antibiotics, specific phages, virulence factor inhibitors, and combination immunotherapy\u2014represent highly promising novel directions. Despite existing challenges, future efforts to deepen mechanistic understanding, develop precision intervention tools, and establish integrated patient stratification systems hold the potential to revolutionize CRC prevention, diagnosis, and combination therapy by targeting\n                    <jats:italic>F. nucleatum<\/jats:italic>\n                    .\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1795703","type":"journal-article","created":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T06:52:54Z","timestamp":1774421574000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["Microbe-driven immune suppression in colorectal cancer: the Fusobacterium nucleatum playbook"],"prefix":"10.3389","volume":"17","author":[{"given":"Wang","family":"Wuyi","sequence":"first","affiliation":[{"name":"Department of Colorectal Surgery, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, Cancer Hospital Affiliated to University of Electronic Science and Technology of China","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pan","family":"Tao","sequence":"additional","affiliation":[{"name":"Department of Colorectal Surgery, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, Cancer Hospital Affiliated to University of Electronic Science and Technology of China","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,25]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"392","DOI":"10.1038\/nm.4517","article-title":"Current understanding of the human microbiome","volume":"24","author":"Gilbert","year":"2018","journal-title":"Nat Med"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-019-0377-7","article-title":"The microbiome, cancer, and cancer 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