A mouse model to assess immunotherapy-related colitis.

Abstract

Combined blockade of the immune checkpoints PD-1 and CTLA-4 has shown remarkable efficacy in patients with melanoma, renal cell carcinoma, non-small-cell lung cancer and mesothelioma, among other tumor types. However, a proportion of patients suffer from serious immune-related adverse events (irAEs). In severe cases, a reduction of the doses or the complete cessation of the treatment is required, limiting the antitumor efficacy of these treatments. Colitis is among the most frequent and problematic irAE associated with immune checkpoint blockade. In this context, animal models that recapitulate the pathophysiological features of immunotherapy-related colitis are needed. In this manuscript, we describe our experience with a mouse model in which the combined CTLA-4 and PD-1 blockade exacerbates the deleterious effects of dextran sulfate sodium (DSS)-induced colitis. This model may constitute a valuable tool for the study of immunotherapy-related colitis.