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Microbial induction of MHC-II expression in colon cancer cells overcomes immunotherapy resistance and limits metastasis

ABSTRACT: We identify commensal microbes that inhibit tumor progression and metastasis, thereby extending survival in four CRC models in two different mouse strains. These microbes exert tumor-suppressive effects by reprogramming the tumor immune microenvironment. This results in improved functionality and increased infiltration of T cells into MSS mCRC, transforming non-immunogenic, 'cold' tumors into immunologically active, 'hot' ones. We demonstrate that the MHC-II antigen presentation pathway in MSS cancer cells is necessary and sufficient for mediating the anti-tumor effects of the microbiome, and enhanced MHC-II on MSS mCRC tumors improves the efficacy of immunotherapy. Furthermore, elevating MHC-II expression on human MSS mCRC organoids significantly improves interactions between cancer and immune cells, leading to more effective cancer clearance in autologous patient-derived organoid-immune cell co-cultures. These findings suggest that modulation of cancer MHC-II expression, such as via microbes, can boost anti-tumor immunity and potentially improve the efficacy of immunotherapy in patients with MSS and mCRC.

ORGANISM(S): Mus musculus

PROVIDER: GSE314209 | GEO | 2026/02/14

REPOSITORIES: GEO

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