Abstract C062: Tryptophan degradation by intestinal <i>Bacteroides</i> induces anti-tumor immunity and limits melanoma growth

Abstract Defining mechanisms used by the gut microbiome to control anti-tumor immunity may offer novel therapeutic modalities. Here, we demonstrate that Bacteroides rodentium and the closely related species Bacteroides uniformis induced anti-tumor immunity and limited melanoma development when colonized in germ-free (GF) mice, in mice with complex microbiome, or in WT mice. Enhanced CD8+ T cell infiltration seen in tumors of mice harboring B. rodentium coincided with increased expression of immune-stimulating pathways. Metabolomic analyses of cecal samples from GF mice colonized with ASF plus B. rodentium revealed lower tryptophan levels compared to ASF colonized controls. Feeding WT mice a tryptophan-deficient diet was sufficient to inhibit melanoma development. In silico genomic reconstruction of metabolic pathways revealed that B. rodentium harbors the tryptophanase A (TnaA) gene, which degrades tryptophan, the ortholog of which is found in B. uniformis. Administration of B. uniformis, which was mutated in TnaA, failed to inhibit melanoma growth in GF mice. Altogether, these findings highlight a novel mechanism of anti-tumor immunity and tumor growth inhibition dependent on tryptophan degradation by intestinal Bacteroides species. Citation Format: Ximena P. Diaz Olea, Kristin Beede, Gabriel Pereira, David Scott, Christopher Pettucci, Eric Martens, Dmitri Rodionov, Hyungsoo Kim, Ashok Kumar Sharma, Anthony Martin, Tongwu Zhang, Suzanne Devkota, Andrei Osterman, Amanda E. Ramer-Tait, Ze'ev A. Ronai. Tryptophan degradation by intestinal Bacteroides induces anti-tumor immunity and limits melanoma growth [abstract]. In: Proceedings of the AACR Immuno-Oncology Conference (AACR IO): Discovery and Innovation in Cancer Immunology: Revolutionizing Treatment through Immunotherapy; 2026 Feb 18-21; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Immunol Res 2026;14(2 Suppl):Abstract nr C062.