Mouse models of immune-related adverse events: progress, challenges, and opportunities

With immune checkpoint inhibitors (ICIs) being an established therapeutic pillar for many cancers, the management of their associated toxicities has emerged as a key clinical challenge. Immune-related adverse events (irAEs) frequently require immunosuppressive therapy, raising the concern that these treatments may dampen the antitumor effects elicited by ICIs. Foundational work in mice enabled the discovery of ICIs, and in this review, we discuss the continued importance of preclinical mouse modeling to understand the molecular mechanisms underpinning the most common irAEs. Mouse models can be used as surrogates to evaluate the effects of immunosuppressive therapies on irAEs, tumor growth, and ICI-mediated antitumor immunity. In reviewing genetic and pharmacological approaches to induce irAEs in mice, we identify key considerations for developing next-generation mouse models of irAEs.