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

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

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

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.

Original languageEnglish
Pages (from-to)1532-1547
Number of pages16
JournalCell Death and Differentiation
Volume28
Issue number5
DOIs
StatePublished - May 2021
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2020, The Author(s).

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