Novel actors on the stage of cardiac dysfunction induced by anti-PD1 oncological treatments

This editorial refers to ‘Targeting early stages of cardiotoxicity from anti-PD1 immune checkpoint inhibitor therapy’, by L. Michel et al., doi:10.1093/eurheartj/ehab430. Cancer immunotherapies with monoclonal antibodies (mAbs) against immune checkpoints [i.e. cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and programmed death 1 (PD1)/programmed death ligand 1 (PDL1)] have dramatically improved antineoplastic treatments. Immune checkpoint inhibitors (ICIs) approved for cancer immunotherapy are the mAbs anti-CTLA-4 (ipilimumab), anti-PD1 (nivolumab, pembrolizumab, cemiplimab, and dostarlimab), and anti-PDL1 (atezolizumab, avelumab, and durvalumab).1,2 Unfortunately, ICI therapies may bring about immune-related adverse events (irAEs), including increased risk of developing myocarditis. The pathophysiological mechanisms of cardiotoxicity induced by ICIs are still to be fully elucidated. PDL1 and PD1 are both expressed on murine and human cardiomyocytes. CTLA-4 and PD1 deletion or inhibition can cause autoimmune myocarditis with lymphocytic infiltration of cytotoxic T cells, suggesting that these molecules have a major role in preventing autoimmunity....