{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:13:56Z","timestamp":1785402836942,"version":"3.56.0"},"posted":{"date-parts":[[2026,5,11]]},"group-title":"Cancer Biology","reference-count":73,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T00:00:00Z","timestamp":1778457600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"award":["R35CA197465"],"award-info":[{"award-number":["R35CA197465"]}],"id":[{"id":"https:\/\/ror.org\/040gcmg81","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R21CA249822"],"award-info":[{"award-number":["R21CA249822"]}],"id":[{"id":"https:\/\/ror.org\/040gcmg81","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,5,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Defining mechanisms used by gut microbiota to control anti-tumor immunity may offer novel therapeutic modalities. Here, we demonstrate that\n                  <jats:italic>Bacteroides rodentium<\/jats:italic>\n                  and closely related\n                  <jats:italic>Bacteroides uniformis<\/jats:italic>\n                  species induce anti-tumor immunity and limit melanoma development when colonized in either germ-free (GF) mice, mice with a complex microbiome, or WT mice. Enhanced CD8\n                  <jats:sup>+<\/jats:sup>\n                  T cell infiltration seen in tumors of mice harboring\n                  <jats:italic>B. rodentium<\/jats:italic>\n                  coincided with increased expression of immune-stimulating pathways and activation of bone marrow-derived dendritic cells that were co-cultured with the\n                  <jats:italic>B. rodentium<\/jats:italic>\n                  secretome. Metabolomic analyses of cecal samples from GF mice colonized with Altered Shedlar Flora (ASF) plus\n                  <jats:italic>B. rodentium<\/jats:italic>\n                  revealed lower tryptophan levels than in ASF-colonized controls, and WT mice fed a tryptophan-deficient diet exhibited inhibition of melanoma development.\n                  <jats:italic>In silico<\/jats:italic>\n                  genomic reconstruction of metabolic pathways revealed that both\n                  <jats:italic>B. rodentium<\/jats:italic>\n                  and\n                  <jats:italic>B. uniformis<\/jats:italic>\n                  harbor tryptophanase A (\n                  <jats:italic>TnaA<\/jats:italic>\n                  ) and aromatic amino transferase (\n                  <jats:italic>ArAT<\/jats:italic>\n                  ) genes, both of which function in tryptophan degradation. Administration of a\n                  <jats:italic>B. uniformis<\/jats:italic>\n                  harboring\n                  <jats:italic>TnaA<\/jats:italic>\n                  mutant failed to inhibit melanoma growth in gnotobiotic mice. Notably, administration of indoles, but not kynurenines, also effectively inhibited melanoma development, increasing immune cell infiltration into the tumors. Correspondingly, levels of bacterially encoded tryptophan-degrading enzymes were higher in cohorts of melanoma patients responding to immune checkpoint blockade. These findings highlight a novel mechanism of anti-tumor immunity and tumor growth inhibition dependent on the tryptophan degradation products, indoles, produced by intestinal\n                  <jats:italic>Bacteroides<\/jats:italic>\n                  species.\n                <\/jats:p>","DOI":"10.64898\/2026.05.06.723300","type":"posted-content","created":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T21:40:12Z","timestamp":1778535612000},"source":"Crossref","is-referenced-by-count":0,"title":["Tryptophan degradation by intestinal Bacteroides induces anti-tumor immunity and limits melanoma growth"],"prefix":"10.64898","author":[{"given":"Ximena","family":"Diaz Olea","sequence":"first","affiliation":[{"name":"Translational Research Institute, Elinor and Rendall Department of Surgery"},{"name":"Department of Biomedical Sciences, Cedars Sinai Medical Center, Los Angeles, CA, 90048"},{"name":"Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, 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19104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Martens","sequence":"additional","affiliation":[{"name":"Department of Microbiology & Immunology, University of Michigan Medical School, Ann Arbor, MI, 48109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dmitri","family":"Rodionov","sequence":"additional","affiliation":[{"name":"Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, 92037"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aagam","family":"Shah","sequence":"additional","affiliation":[{"name":"Translational Research Institute, Elinor and Rendall Department of Surgery"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel P.","family":"Martinez","sequence":"additional","affiliation":[{"name":"Division of Molecular Oncology & Immunology, the Netherlands Cancer Institute, Amsterdam 1066 CX, The 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