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- Title
Colon Immune-Related Adverse Events: Anti-CTLA-4 and Anti-PD-1 Blockade Induce Distinct Immunopathological Entities.
- Authors
Coutzac, Clélia; Adam, Julien; Soularue, Emilie; Collins, Michael; Racine, Antoine; Mussini, Charlotte; Boselli, Lisa; Kamsukom, Nyam; Mateus, Christine; Charrier, Mélinda; Cassard, Lydie; Planchard, David; Ribrag, Vincent; Fizazi, Karim; Loriot, Yohann; Lepage, Patricia; Scoazec, Jean-Yves; Robert, Caroline; Carbonnel, Franck; Chaput, Nathalie
- Abstract
Background and Aim: Immune checkpoint inhibitors targeting CTLA-4 and PD-1 improve survival in cancer patients but may induce immune-related adverse events, including colitis. The immunological characteristics of anti-CTLA-4 [αCTLA-4]- and anti-PD-1 [αPD-1]-related colitis have been poorly described. The aim of the present study was to compare the immunological and histological characteristics of αCTLA-4-induced colitis and αPD-1-induced colitis. Methods: Colonic biopsies from patients with αCTLA-4-induced colitis, αPD-1-induced colitis, and inflammatory bowel disease [IBD] were analysed by immunohistochemistry and flow cytometry. Tumour necrosis factor alpha [TNFα] concentration was assessed in biopsy supernatants. Results: CD8+ T cells were found in the lamina propria and epithelium in αPD-1-induced colitis, whereas CD4+ T cells were found in the lamina propria in αCTLA-4-induced colitis. No or low intraepithelial lymphocytes were observed in αCTLA-4-induced colitis. No difference in numbers of mucosal regulatory T cells was observed between αCTLA-4- or αPD-1-induced colitis and IBD patients. Higher numbers of activated ICOS+ conventional CD4+ T cells were observed in αCTLA- 4-induced colitis compared with patients with IBD. Among ICOS+CD4+ T cells, conventional CD4+ T cells were the main T cell population in patents with αCTLA-4-induced colitis, whereas Treg cells were predominant in IBD or αPD-1-induced colitis. High mucosal TNFα concentrations were observed in αCTLA-4-induced colitis. Low mucosal TNFα concentrations were associated with steroid sensitivity. Conclusions: These observations show that αCTLA-4- and αPD-1-induced colitis have distinct immunological characteristics. Mucosal TNFα concentration might detect patients at risk of developing corticosteroid resistance after CTLA-4 blockade.
- Publication
Journal of Crohn's & Colitis, 2017, Vol 11, Issue 10, p1238
- ISSN
1873-9946
- Publication type
Article
- DOI
10.1093/ecco-jcc/jjx081