SITC 2022 | Immune-mediated mechanisms in checkpoint inhibitor-induced myocarditis

Han Zhu, MD, Stanford University, Standford, CA, talks on an investigation into immune-mediated mechanisms in checkpoint inhibitor-induced myocarditis. Blood was collected from three patient groups. Group A included patients who received immunotherapy and did not have any side effects. Group B developed noncardiac autoimmunity’s, such as hepatitis, following immunotherapy. Group C received immunotherapy and then developed myocarditis. Single-cell multiomics was performed on the blood, including single-cell RNA sequencing and single-cell TCR sequencing. The blood of the patients who had myocarditis had expansion of a particular type of T-cell, TEMRA CD8 T-cell, that exhibit characteristics suggestive of a role in the disease and activation of different pathways of autoimmunity. Studies using mouse models were used to investigate the mechanism of how these T-cells may be contributing to the disease. The mice were also observed to have an expansion of cytotoxic effector CD8 T-cells. These T-cells are clonally expanded and targeted to a certain antigen that is suspected to be located in the heart. This interview took place at the 37th Annual Meeting of the Society for Immunotherapy in Cancer (SITC 2022) in Boston, MA.

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