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Sept 24th: Linda Bilonda Mutala
24 September @ 13 h 30 min - 14 h 30 min UTC+1
CRCINA Equipe , Nantes
Title: The inflammasome of tumor cells in colorectal cancer : status and role in modulating tumor infiltrating T lymphocytes (TILs)
Immune checkpoint inhibitors improve the overall survival of a limited number of colorectal cancer (CRC) patients. Identifying pathways that influence the immunological anti-tumor response to treatment is critical to improve the therapeutic efficacy and predict clinical responses. Among these pathways, the inflammasome is an emerging player in cancer immunology. An innate immunity platform, the inflammasome is present in normal human intestinal epithelial cells but its status in CRC tumor cells and its role in modulating adaptive immunity remain unclear. Using patient-derived colon explant cultures, we show that, in the majority of CRC patients, the inflammasome of tumor cells retains a functional but aberrantly activated caspase-1/IL-18 axis and contributes to drive a Th1/Tc1 response elicited by TILs expressing IL-18Ra. Furthermore, unsupervised clustering identified 3 clusters of CRC patients with distinct caspase-1/IL-18/TIL density/IFNg axes and microsatellite status. Together, our results suggest that the inflammasome could be a target to improve the anti-tumor Th1/Tc1 response in CRC.