{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T00:21:31Z","timestamp":1783556491394,"version":"3.55.0"},"posted":{"date-parts":[[2024,8,15]]},"group-title":"Immunology","reference-count":50,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2024,8,15]],"date-time":"2024-08-15T00:00:00Z","timestamp":1723680000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,8,14]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  Therapies that harness the immune system to target and eliminate tumor cells have revolutionized cancer care. Immune checkpoint blockade (ICB), which boosts the anti-tumor immune response by inhibiting negative regulators of T cell activation\n                  <jats:sup>1\u20133<\/jats:sup>\n                  , is remarkably successful in a subset of cancer patients, yet a significant proportion do not respond to treatment, emphasizing the need to understand factors influencing the therapeutic efficacy of ICB\n                  <jats:sup>4\u20139<\/jats:sup>\n                  . The gut microbiota, consisting of trillions of microorganisms residing in the gastrointestinal tract, has emerged as a critical determinant of immune function and response to cancer immunotherapy, with multiple studies demonstrating association of microbiota composition with clinical response\n                  <jats:sup>10\u201316<\/jats:sup>\n                  . However, a mechanistic understanding of how gut commensal bacteria influence the efficacy of ICB remains elusive. Here we utilized a gut commensal microorganism, segmented filamentous bacteria (SFB), which induces an antigen-specific Th17 cell effector program\n                  <jats:sup>17<\/jats:sup>\n                  , to investigate how colonization with it affects the efficacy of ICB in restraining distal growth of tumors sharing antigen with SFB. We find that anti-PD-1 treatment effectively inhibits the growth of implanted SFB antigen-expressing melanoma only if mice are colonized with SFB. Through T cell receptor clonal lineage tracing, fate mapping, and peptide-MHC tetramer staining, we identify tumor-associated SFB-specific Th1-like cells derived from the homeostatic Th17 cells induced by SFB colonization in the small intestine lamina propria. These gut-educated ex-Th17 cells produce high levels of the pro-inflammatory cytokines IFN-\u03b3 and TNF-\u03b1, and promote expansion and effector functions of CD8\n                  <jats:sup>+<\/jats:sup>\n                  tumor-infiltrating cytotoxic lymphocytes, thereby controlling tumor growth. A better understanding of how distinct intestinal commensal microbes can promote T cell plasticity-dependent responses against antigen-sharing tumors may allow for the design of novel cancer immunotherapeutic strategies.\n                <\/jats:p>","DOI":"10.1101\/2024.08.12.607605","type":"posted-content","created":{"date-parts":[[2024,8,15]],"date-time":"2024-08-15T05:20:11Z","timestamp":1723699211000},"source":"Crossref","is-referenced-by-count":3,"title":["Microbiota-induced plastic T cells enhance immune control of antigen-sharing tumors"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2693-5248","authenticated-orcid":false,"given":"Tariq A.","family":"Najar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1588-0587","authenticated-orcid":false,"given":"Yuan","family":"Hao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1810-0822","authenticated-orcid":false,"given":"Yuhan","family":"Hao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-0984-3370","authenticated-orcid":false,"given":"Gabriela","family":"Romero-Meza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Dolynuk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2850-8688","authenticated-orcid":false,"given":"Dan R.","family":"Littman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2024081613201456000_2024.08.12.607605v1.1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aar4060"},{"key":"2024081613201456000_2024.08.12.607605v1.2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3239"},{"key":"2024081613201456000_2024.08.12.607605v1.3","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-020-0306-5"},{"key":"2024081613201456000_2024.08.12.607605v1.4","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaa8172"},{"key":"2024081613201456000_2024.08.12.607605v1.5","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1003466"},{"key":"2024081613201456000_2024.08.12.607605v1.6","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1200690"},{"key":"2024081613201456000_2024.08.12.607605v1.7","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1504627"},{"key":"2024081613201456000_2024.08.12.607605v1.8","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.09.020"},{"key":"2024081613201456000_2024.08.12.607605v1.9","doi-asserted-by":"publisher","DOI":"10.1038\/nrc.2016.2"},{"key":"2024081613201456000_2024.08.12.607605v1.10","doi-asserted-by":"publisher","DOI":"10.1126\/science.aad1329"},{"key":"2024081613201456000_2024.08.12.607605v1.11","doi-asserted-by":"publisher","DOI":"10.1126\/science.aac4255"},{"key":"2024081613201456000_2024.08.12.607605v1.12","doi-asserted-by":"publisher","DOI":"10.1126\/science.aan3706"},{"key":"2024081613201456000_2024.08.12.607605v1.13","doi-asserted-by":"publisher","DOI":"10.1126\/science.aan4236"},{"key":"2024081613201456000_2024.08.12.607605v1.14","doi-asserted-by":"publisher","DOI":"10.1126\/science.aao3290"},{"key":"2024081613201456000_2024.08.12.607605v1.15","doi-asserted-by":"publisher","DOI":"10.1126\/science.abb5920"},{"key":"2024081613201456000_2024.08.12.607605v1.16","doi-asserted-by":"publisher","DOI":"10.1126\/science.abf3363"},{"key":"2024081613201456000_2024.08.12.607605v1.17","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.09.033"},{"key":"2024081613201456000_2024.08.12.607605v1.18","doi-asserted-by":"publisher","DOI":"10.1186\/s40425-019-0650-9"},{"key":"2024081613201456000_2024.08.12.607605v1.19","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2020.04.044"},{"key":"2024081613201456000_2024.08.12.607605v1.20","doi-asserted-by":"publisher","DOI":"10.1038\/S41591-021-01655-5"},{"key":"2024081613201456000_2024.08.12.607605v1.21","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaz7015"},{"key":"2024081613201456000_2024.08.12.607605v1.22","doi-asserted-by":"publisher","DOI":"10.1126\/science.aar6918"},{"key":"2024081613201456000_2024.08.12.607605v1.23","doi-asserted-by":"publisher","DOI":"10.1126\/science.aax0701"},{"key":"2024081613201456000_2024.08.12.607605v1.24","doi-asserted-by":"publisher","DOI":"10.1126\/science.abp9563"},{"key":"2024081613201456000_2024.08.12.607605v1.25","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2023.11.003"},{"key":"2024081613201456000_2024.08.12.607605v1.26","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-101320-011829"},{"key":"2024081613201456000_2024.08.12.607605v1.27","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2010.06.001"},{"key":"2024081613201456000_2024.08.12.607605v1.28","doi-asserted-by":"publisher","DOI":"10.1038\/nature23910"},{"key":"2024081613201456000_2024.08.12.607605v1.29","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-06026-3"},{"key":"2024081613201456000_2024.08.12.607605v1.30","doi-asserted-by":"publisher","DOI":"10.1038\/nature13279"},{"key":"2024081613201456000_2024.08.12.607605v1.31","doi-asserted-by":"publisher","DOI":"10.1080\/2162402X.2018.1456612"},{"key":"2024081613201456000_2024.08.12.607605v1.32","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abe3348"},{"key":"2024081613201456000_2024.08.12.607605v1.33","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.05.017"},{"key":"2024081613201456000_2024.08.12.607605v1.34","doi-asserted-by":"publisher","DOI":"10.1126\/science.aav3487"},{"key":"2024081613201456000_2024.08.12.607605v1.35","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.135597"},{"key":"2024081613201456000_2024.08.12.607605v1.36","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aan2306"},{"key":"2024081613201456000_2024.08.12.607605v1.37","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aaj1921"},{"key":"2024081613201456000_2024.08.12.607605v1.38","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1600737"},{"key":"2024081613201456000_2024.08.12.607605v1.39","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.08.061"},{"key":"2024081613201456000_2024.08.12.607605v1.40","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.00814-09"},{"key":"2024081613201456000_2024.08.12.607605v1.41","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2018.03.018"},{"key":"2024081613201456000_2024.08.12.607605v1.42","doi-asse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