Ileal immune tonus is a prognosis marker of proximal colon cancer in mice and patients

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Picard, Marion | Yonekura, Satoru | Slowicka, Karolina | Petta, Ioanna | Rauber, Conrad | Routy, Bertrand | Richard, Corentin | Iebba, Valerio | Tidjani Alou, Maryam | Becharef, Sonia | Ly, Pierre | Pizzato, Eugenie | Lehmann, Christian | Amon, Lukas | Klein, Christophe | Opolon, Paule | Gomperts Boneca, Ivo | Scoazec, Jean-Yves | Hollebecque, Antoine | Malka, David | Ghiringhelli, François | Dudziak, Diana | Berx, Geert | Vereecke, Lars | van Loo, Geert | Kroemer, Guido | Zitvogel, Laurence | Roberti, Maria Paula

Edité par CCSD ; Nature Publishing Group -

International audience. Ileal epithelial cell apoptosis and the local microbiota modulate the effects of oxaliplatin against proximal colon cancer by modulating tumor immunosurveillance. Here, we identified an ileal immune profile associated with the prognosis of colon cancer and responses to chemotherapy. The whole immune ileal transcriptome was upregulated in poor-prognosis patients with proximal colon cancer, while the colonic immunity of healthy and neoplastic areas was downregulated (except for the Th17 fingerprint) in such patients. Similar observations were made across experimental models of implanted and spontaneous murine colon cancer, showing a relationship between carcinogenesis and ileal inflammation. Conversely, oxaliplatin-based chemotherapy could restore a favorable, attenuated ileal immune fingerprint in responders. These results suggest that chemotherapy inversely shapes the immune profile of the ileum–tumor axis, influencing clinical outcome.

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