Tang and colleagues show that a half-life-extended IL-10–Fc fusion protein acts directly on terminally exhausted PD1+TIM-3+CD8+ T cells to enhance their proliferation and effector function by reprogramming the cellular metabolism to oxidative phosphorylation in a mitochondrial pyruvate carrier–dependent manner. Treatment of tumor-bearing mice with IL-10–Fc and adoptive T cell therapy led to eradication of their established solid tumors and durable cures.
- Yugang Guo
- Yu-Qing Xie
- Li Tang
