Immune-related toxicities of checkpoint inhibitors: mechanisms and mitigation strategies

In this Review, Weber and Sullivan discuss the different types of immune-related adverse events associated with checkpoint inhibitors and how their treatment may shed light on their mechanisms and possible strategies and targets for prophylactic and therapeutic interventions to mitigate them. The immune-related adverse events associated with treatment with immune checkpoint inhibitors result in significant morbidity for patients as well as considerable cost to the health-care system, and can limit the use of these beneficial drugs. Understanding the mechanisms of these side effects and how they can be separated from the antitumour effects of immune checkpoint inhibitors, as well as identifying biomarkers that predict the development of immune-related toxicities, will facilitate the conduct of trials to limit their onset and improve patient outcomes. In this Review, we discuss the different types of immune-related adverse events and how their treatment and identification of possible predictive biomarkers may shed light on their mechanisms, and describe possible strategies and targets for prophylactic and therapeutic intervention to mitigate them.