Gut Microbiota Conditioning Promotes Anti-Tumor Immunity and Responsiveness to Immunological Checkpoint Blockade in Colorectal Cancer

Abstract Background Colorectal cancer (CRC) infiltration by T lymphocytes is associated with prolonged survival. However, immune spontaneously occurs in <20% of tumors and no therapies able to promote it are currently available. CRC tissue populated gut bacteria translocated across the neoplastic epithelium. We previously showed that direct contact between tumor cells induces overexpression genes encoding cell-recruiting chemokines cells, we identified a panel bacterial species enhanced chemokine expression, high cell favorable prognosis. Aims In this project tested ability boost T-cell regression orthotopic experimental models. Methods Luciferase-expressing mismatch repair (MMR)-proficient or -deficient murine from established lines were injected intra-cecum syngeneic mice. Tumor growth was monitored bioluminescence. Bacterial interest, defined as Operational Taxonomic Units (OTUs), cultured under anaerobic conditions, and, following development, administered tumor-bearing mice oral gavage. specific experiments, administration combined immunological checkpoint blockade (ICB), based on injection anti-PD-1 antibodies. Immune evaluated flow cytometry, harvesting enzymatic digestion. Results MMR-deficient tumors, known be immunogenic responsive immunotherapy, OTU8, sufficient reduce growth. MMR-proficient scarcely infiltrated poorly ICB, did not per se affect growth, but cytotoxic CD8+ ultimately leading, combination antibodies, inhibition. Conclusions demonstrated promotes endogenous responses against CRC. Gut microbiota conditioning might represent an innovative therapeutic strategy enhance responsiveness ICB broaden its indication beyond tumors.