Ileal immune tonus is a prognosis marker of proximal colon cancer in mice and patients
Marion Picard, Satoru Yonekura, Karolina Slowicka, Ιωάννα Πέττα, Conrad Rauber, Bertrand Routy, Corentin Richard, Valerio Iebba, Maryam Tidjani Alou, Sonia Becharef, Pierre Ly, Eugénie Pizzato, Christian H.K. Lehmann, Lukas Amon, Christophe Klein, Paule Opolon, Ivo G. Boneca, Jean‐Yves Scoazec, Antoine Hollebecque, David Malka, François Ghiringhelli, Diana Dudziak, Geert Berx, Lars Vereecke, Geert Loo, Guido Kroemer, Laurence Zitvogel, María Paula Roberti
Abstract
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.