T cells specific for α-myosin drive immunotherapy-related myocarditis.

ABSTRACT: Immune-related adverse events, particularly severe toxicities such as myocarditis, are major challenges to the utility of immune checkpoint inhibitors (ICIs) in anticancer therapy¹. The pathogenesis of ICI-associated myocarditis (ICI-MC) is poorly understood. Pdcd1^-/-Ctla4^+/- mice recapitulate clinicopathological features of ICI-MC, including myocardial T cell infiltration². Here, using single-cell RNA and T cell receptor (TCR) sequencing of cardiac immune infiltrates from Pdcd1^-/-Ctla4^+/- mice, we identify clonal effector CD8⁺ T cells as the dominant cell population. Treatment with anti-CD8-depleting, but not anti-CD4-depleting, antibodies improved the survival of Pdcd1^-/-Ctla4^+/- mice. Adop

SUBMITTER: Axelrod ML 

PROVIDER: S-EPMC9930174 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature