Testing Immune-Related Adverse Events in Cancer Immunotherapy

Abstract

Immune-targeted therapeutics are being used in cancer. Immune "checkpoint inhibition" provides promise for prolonged disease-free patient survival. Use of immune checkpoint inhibitors in cancer has coincided with the onset of immune-related adverse events (irAEs). irAEs are caused by a break in host self-tolerance, which can be deadly. Acute management of irAEs is complicated by difficulty making a prompt clinical diagnosis. The goal is to maximize anticancer benefit while minimizing irAE risk. We currently lack diagnostic tools to assess pretreatment irAE risk and facilitate diagnosis. Current immunologic understanding of irAEs is discussed with an emphasis on how patients with congenital syndromes of T-cell activation may inform this understanding. The prospects of improving diagnostics for and treatment of irAEs are discussed.

Keywords: CTLA-4; Immune checkpoint inhibitor; Immune-related adverse event; LRBA.