Targeting negative regulators of immunity with immune-checkpoint inhibitors (ICIs) has led to significant survival benefit in patients with various cancer entities. ICI therapy disrupts mechanisms of immune tolerance, which induces inflammatory toxicities in different target organs, summarized as immune-related adverse events (irAEs) in some patients. ICI-colitis relies on the activation of intestinal tissue-resident memory T cells (TRM cells) and is one of the most frequently observed immune-related toxicities; it can be fatal if untreated. The disease is associated with highly cytotoxic intestinal T cells and inflammatory myeloid activation. Current clinical management relies on broad immunosuppression, potentially reducing antitumor immunity. Ideal future therapies for irAEs will uncouple immunosuppressive activities in the inflamed target organ and the tumor microenvironment.
Braun et al. (Fri,) studied this question.