Stocking the toolbox—Using preclinical models to understand the development and treatment of immune checkpoint inhibitor-induced immune-related adverse events

Cancer patients treated with immune checkpoint inhibitors (ICIs) are susceptible to a broad and variable array of immune-related adverse events (irAEs). With increasing clinical use of ICIs, defining the mechanism for irAE development is more critical than ever. However, it currently remains challenging to predict when these irAEs occur and which organ may be affected, and for many of the more severe irAEs, inaccessibility to the tissue site hampers mechanistic insight. This lack of understanding of irAE development in the clinical setting emphasizes the need for greater use of preclinical models that allow for improved prediction of biomarkers for ICI-initiated irAEs or that validate treatment options that inhibit irAEs without hampering the anti-tumor immune response. Here, we discuss the utility of preclinical models, ranging from exploring databases to in vivo animal models, focusing on where they are most useful and where they could be improved.