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.

Source:
Journal reference:

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.

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