Table 1.

Unique characteristics of CPI-induced irAEs observed in the clinic that aid in understanding immune mechanism

irAEAutoimmune vs. autoinflammatoryPreclinical and translational mechanistic evidenceSevere irAE treatmentEvidence of improved clinical objective response
Anti–CTLA-4 predominant irAE
 ColitisAutoinflammatoryT-cell repertoire diversification (44), Treg depletion (32), increased IL17 (46), increased neutrophil gene signature and infiltrate (74)Corticosteroids, infliximab, vedolizumab (9)Yes (57)
 HypophysitisAutoimmuneCTLA-4 expression on pituitary gland initiating activation of complement (10, 37)Hormone replacementYes (56)
Anti–PD-1/PD-L1 predominant irAE
 Diabetes mellitusAutoimmunePD-L1 expression on stressed beta cells (35)InsulinSuggested with limited evidence (39)
 HypothyroidismAutoimmuneAutoantibody amplification (6)Hormone replacementYes (6)
 PneumonitisAmbiguousUnknownCorticosteroid, infliximab or cyclophosphamide, mycophenolate mofetil or IVIg (9)Suggested with limited evidence (75)
 MyocarditisAutoimmuneShared tumor and organ-specific neoantigen (12)Corticosteroids, IVIg, plasmapheresis (9)Difficult to assess given irAE-related mortality
Melanoma patients
 VitiligoAutoimmuneShared tumor and self-antigens (55)NoneYes (55)
  • Abbreviations: CTLA-4, cytotoxic T-lymphocyte–associated protein-4; irAE, immune-related adverse event; IVIg, intravenous immunoglobulin; PD-1, programmed death-1; PD-L1, programmed death-ligand 1; Treg, regulatory T cell.