T cells play important roles in antitumor immunity but they are often functionally exhausted in tumour microenvironment.Here we report a new anti-exhaustion mechanism in T cells.Phospholipid Scramblase 1(PLSCR1),a membrane protein that can activate the PI3K-AKT pathway,can suppress PD-1 transcription to enhance T cell antitumor immunity.PLSCR1 has induced expression upon T cell activation and it can recruit PI3K to activate the AKT-Foxo pathway to enhance T cell effector function and suppress PD-1 expression.PLSCR1 deficiency led to higher T cell exhaustion in the tumor microenvironment.Overexpressing PLSCR1 in CD8+T cells led to enhanced effector function and lower PD-1 expression.The antitumor effect of PLSCR1over-expCD8+T cells was significantly better than wildtype cells in an adoptive T cell therapy to treat mouse melanoma.Our results identify a new signaling molecule in T cells and present a new means to enhance T-cell antitumor immunity.