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He Research Summary

Identification of the mechanism of anti-PD1 immunotherapies induced cardiac/pulmonary inflammation and injury during heart failure. Programmed death[1]1 (PD1) plays an important role in the inhibitory effects on T cell function and immunosuppressive function of T regulatory cells. Anti-PD1 immunotherapies are effective in treating various cancers, but also cause cardiovascular adverse events through unknown mechanism. T cells activation is governed by metabolic reprogramming that switches from oxidative phosphorylation (OXPHOS) and fatty acid oxidation (FAO) to aerobic glycolysis for proper effector functions. PD1 blocked T-effector cell differentiation by inhibiting glycolysis and promoting fatty acid oxidation (FAO). While PD1 knockout (KO) or PD1 blocking antibodies have no detectable effect on cardiac inflammation and function in normal mice, we found that PD1 KO or inhibition dramatically exacerbated pressure overload (PO)-induced cardiac/lung inflammation, heart failure (HF) and death. Therefore, an important aim of our research is to better understand the metabolic profile of the T cells during HF and the mechanism by which PD-1 inhibition mediated cardiac/lung inflammation.