Immune and autoimmune-related adverse events associated with immune checkpoint inhibitors in cancer therapy

The recent development of monoclonal antibodies that disinhibit the immune system from recognizing and attacking tumor cells has revolutionized the treatment of cancer. Among these agents are drugs that specifically block cytotoxic T-lymphocyte protein 4 (CTLA-4), programmed cell death protein 1 (PD-1) and programmed cell death 1 ligand 1 (PD-L1) signaling, called immune checkpoint inhibitors (ICIs). While these agents are generally well tolerated, ICI therapy can lead to loss of self-tolerance and the development of autoimmunity, manifesting as immune-related adverse events (IRAEs). Although potentially linked to increased antitumor responses, the morbidity associated with IRAEs can be significant and in rare circumstances, fatal. Virtually any organ can be affected and the patients present with a broad range of signs and symptoms. Moreover, ICIs have varying IRAEs and have distinct toxicity profiles based on their mechanism of action. Fortunately, most of the IRAEs can be managed with immunosuppression and supportive care, but contingent on early recognition and prompt treatment. With increasing advances in drug development, including combination ICI therapy, these agents are becoming one of the most prescribed oncology drugs and clinicians should be knowledgeable about the recognition and management of IRAEs.