PSGL-1 immune checkpoint expression reshapes the anti-tumor immune response in anti-PD-1-resistant melanoma 4045

Abstract Description Despite the clinical success of standard of care immunotherapies targeting PD-1/L1 and/or CTLA-4 by immune checkpoint blockade (ICB), almost two thirds of melanoma patients do not respond. This disparity in clinical efficacy highlights the need to explore alternative targets for immunotherapy of anti-PD-1 resistant melanoma. Recent reports demonstrate that inhibiting the immune checkpoint P-selectin glycoprotein ligand-1 (PSGL-1) by ICB improves tumor control in preclinical melanoma models, but there is a need for a better understanding of how targeting PSGL-1 reshapes the global anti-tumor immune response to anti-PD-1 resistant melanoma. In this study, we test the central hypothesis that PSGL-1 immune checkpoint expression alters immune cell dynamics in the melanoma tumor microenvironment (TME). Here, we performed spectral flow cytometry analysis on D4M-3A melanoma tumors in wildtype (WT) or PSGL-1-KO (KO) mice. We show PSGL-1 expression across most immune populations in the TME, with the highest expression in T cells and NK cells. Additionally, we found high expression of the PSGL-1 binding partner VISTA on most immune cells in the TME. We found that PSGL-1 KO mice had increased antigen presenting cells and effector T cells, and cDCs displayed increased MHC-II expression. Our data suggests that PSGL-1 reshapes both innate and adaptive immune cells in the TME. Funding Sources Supported by NIH/NIAMS T32 Training Award AR080622; NIH/NIAID R01 AI137239; Dept. of Def. HT9425-23-1-1020. Topic Categories Tumor Immunology: Cellular Responses and Tumor Microevironment (TIME)