Moving towards personalized treatments of immune-related adverse events

The treatment of immune-related adverse events (irAEs) in patients receiving immune checkpoint inhibitors has mostly been based on adapting therapeutic approaches used in the management of primary autoimmune diseases. The authors of this Review provide an overview of the different cellular and soluble immune factors involved in the pathogenesis of irAEs in order to help clinicians deliver personalized immunopathologically guided treatment to manage these adverse events. The enhancement of immune responses upon treatment with immune checkpoint inhibitors can have the desired outcome of reinvigorating antitumour immune surveillance, but often at the expense of immune-related adverse events (irAEs). This novel disease entity often prompts comparisons with, and extrapolation of treatment approaches from, primary autoimmune disorders. Accordingly, current treatment guidelines for irAEs make generic recommendations adapted from the literature describing primary autoimmune diseases, without taking into consideration the substantial disparity of the immunohistopathological findings within each organ affected by an irAE. The treatment modalities themselves are complex and have many potential drawbacks, such as serious and rarely fatal infections, drug toxicities overlapping with irAEs and the risk of compromising cancer immune surveillance. Herein, we provide an overview of key cellular and soluble immunological factors mediating irAEs and propose a model integrating this knowledge with the immunohistopathological findings of the affected organs for a personalized decision-making process for each patient.