Role of the E3 ubiquitin ligase Peli1 in regulating antitumor T cell responses

Abstract Metabolic fitness of T cells is crucial for immune responses against infections and tumorigenesis. Both the cell receptor signal (TCR) environmental cues contribute to induction metabolic reprogramming, but underlying mechanism incompletely understood. Here, we identified E3 ubiquitin ligase Peli1 as an important regulator metabolism antitumor immunity. ablation profoundly promotes tumor rejection, associated with increased effector function number tumor-infiltrating CD4 CD8 cells. Moreover, deficiency inhibited expression PD-1 TIM-3 reduced exhaustion The Peli1-deficient display markedly stronger activities, particularly glycolysis, than wild-type controls activation mTOR signaling, stimulated by both TCR growth factors, this mediated through regulation mTORC1-inhibitory proteins, TSC1 TSC2. mediates non-degradative ubiquitination TSC1, thereby promoting stabilization TSC complex. These results establish a novel mTORC1 downstream mTORC1-mediated actions on