Immune mechanisms of toxicity from checkpoint inhibitors

Inflammatory toxicities are an important limitation on all checkpoint inhibitor therapies.The spectrum of toxicities differs depending on the specific checkpoint pathway inhibited [e.g., cytotoxic T lymphocyte antigen (CTLA)-4 vs. programmed death (PD)-1].Checkpoint inhibitor toxicities at mucosal surfaces are associated with expansion and activation of resident memory cells.The immune targets of checkpoint inhibitor toxicities are unknown and may be toxicity dependent (e.g., the microbiome for colitis and muscles proteins for myocarditis).Circulating effector memory cells may indicate an elevated risk of checkpoint inhibitor toxicity. Immunotherapy has changed the treatment landscape for cancer over the past…

• AC
  American Cancer Society
• EL
  Eli Lilly and Company
• MR
  Melanoma Research Alliance

  Award: R01AI169188
• NI
  National Institute of Allergy and Infectious Diseases