Immune-related adverse events of checkpoint inhibitors: Insights into immunological dysregulation

Immune checkpoint inhibitors (ICIs) targeting against programmed cell death-1(PD-1) and cytotoxic T-lymphocyte antigen-4 (CTLA-4) have shown efficacy in cancer treatment. However, a spectrum of immune-related adverse events (irAEs) have raised concerns about their clinical application. IrAEs are distinct from traditional chemo- and radiotherapy-induced toxicities, as they are related in particular to the dysregulation of immune system and autoimmunity. The underlying pathogenesis of irAEs remains elusive. Understanding of the potential underlying mechanism is of great importance for the management of irAEs and the development of new ICIs with insignificant irAEs. In this review, we summarize the current evidence to provide insights into the biological basis of irAEs and provide a potential explanation for their pathogenesis, with focus on the relationship between checkpoint molecules and immune cell regulation.