Abstract
To limit excessive T cell-mediated inflammatory responses, the immune system has a milieu of inhibitory receptors, called immune checkpoints. Cancer cells have evolved to seize those inhibitory pathways and to prevent T cell-mediated killing of tumor cells. Therefore, immune checkpoint inhibitors (ICI) consisting of blocking antibodies against these receptors present an exciting avenue in the fight against cancer. The last decade has seen the implementation of ICI against a variety of cancer indications that have improved the overall anti-tumor responses and patient survival. However, inflammatory toxicities and autoimmunity are a significant adverse event of ICI therapies. In this review, we will discuss the biology of immune checkpoints, highlight research strategies that may help reduce the incidence of immune-related adverse events associated with ICI therapies, and also suggest investigational approaches to manipulate immune checkpoints to treat primary autoimmune disorders.