Immune mechanisms of toxicity from checkpoint inhibitors

Immunotherapy has changed the treatment landscape for cancer over the past decade. Inhibitors of the immune checkpoint proteins cytotoxic T lymphocyte antigen (CTLA)-4, programmed death (PD)-1, and PD ligand 1 (PD-L1) can induce durable remissions in a subset of patients with metastatic disease. However, these treatments can be limited by inflammatory toxicities that can affect any organ system in the body and in some cases can be life threatening. Considerable progress has been made in understanding the drivers of these toxicities as well as effective management strategies. Further research into understanding the molecular and cellular mechanisms that drive toxicity will enable better prediction of toxicity and development of optimized therapies for these toxicities that avoid interfering with antitumor immunity. In this review, we discuss our current understanding of the inflammatory toxicities from immune checkpoint inhibitors (ICIs) and propose optimal treatment strategies for these toxicities.