New research uncovers mechanisms behind heart damage from CTLA-4 blockade

Cytotoxic T-lymphocyte antigen 4 (CTLA-4) is a protein receptor on T immune cells that prevents the cells from killing other cells, such as cancer cells. Blocking CTLA-4 with a specific antibody is an effective treatment for some cancers, but it can damage the heart. New research published in The FASEB Journal reveals the mechanisms involved in this side effect-;a finding that could be used to help prevent it.

Experiments conducted in mice showed that blocking CTLA-4 activates certain T cells called Th17 cells, which increase inflammation. Inhibiting this activation reversed anti-CTLA-4–mediated heart damage. " Targeting this axis could potentially offer a preventive or therapeutic strategy for managing cardiotoxicity in patients undergoing anti-CTLA-4-based immune checkpoint inhibitor therapy," the authors wrote.

Wiley Shang , A-Q., et al. (2024) Blocking CTLA-4 promotes pressure overload-induced heart failure via activating Th17 cells.

FASEB Journal . doi.org/10.

1096/fj.202400384R ..