The adhesion molecule PSGL-1 is a checkpoint regulator that promotes T cell dysfunction in melanoma tumors

Abstract

The tumor microenvironment can promote tumor growth by suppressing effector T cell responses. Using a melanoma model that recapitulates aspects of human disease, we investigated the role of the adhesion molecule, P-selectin glycoprotein ligand-1 (PSGL-1) in tumor infiltrating lymphocytes (TILs). We found that PSGL-1 was highly expressed on TILs that also expressed high PD-1 and TIM-3 inhibitory receptors. PSGL-1-deficiency did not impact T cell recruitment in tumors but instead resulted in a greater TIL accumulation. Furthermore, PSGL-1-deficient T cells had reduced PD-1 expression and increased production of effector cytokines that resulted in delayed tumor growth. We did not find differences in Treg recruitment but instead had an increased effector to Treg ratio in tumors. Our findings show that PSGL-1 does not have a nonredundant role in the trafficking of TILs into melanoma tumors, but can act as an immune checkpoint inhibitor to limit anti-tumor T cell responses in the tumor microenvironment thereby promoting tumor growth.