Immune checkpoint inhibitor (ICI) therapies, such as anti-PD1 and anti-CTLA4, have proved to be clinically effective in numerous malignant diseases due to their ability to maintain immune surveillance of tumors by overriding the mechanisms in which lymphocytes establish peripheral tolerance. However, these therapies act in a systematic manner and thus may lead to autoimmune-like side effects termed immune-related adverse events (irAEs) in many organ systems that can ultimately halt treatment or lead to death. Therefore, understanding the underlying drivers of these irAEs is imperative in ensuring the quality of life and safety of our patients on ICI.