PD-1 immune checkpoint blockade can synergize with PSGL-1 inhibition to reinvigorate exhausted T cells

Abstract P-selectin glycoprotein ligand-1 (PSGL-1) is an immune checkpoint regulator that highly expressed on T cells. PSGL-1- deficient mice infected with chronic lymphocytic choriomeningitis virus (LCMV) were shown to control viral infection due increased effector function by anti-viral However, the cell-intrinsic role of PSGL-1 expression CD4 +and CD8 +T cell exhaustion not fully known. Using adoptive transfers WT or PSGL-1-deficient TCR transgenic cells in LCMV, we characterized differentiation and response. We found expansion early during infection, however, at later stages functionally exhausted. exhausted +PSGL-1-deficient reinvigorated more effectively than after PD-L1 blockade their proliferation, cytokine production, accumulation. also observed responses melanoma tumors. Our findings showed was required for maintenance both +exhausted deletion synergized PD-1 reinvigorate these These highlight important reinvigoration T32 AI 141346 R01 AI13723