Antibody blockade of the PSGL-1 immune checkpoint enhances T-cell responses to B-cell lymphoma

Abstract

Despite advancements in cancer immunotherapy, most lymphomas remain unresponsive to checkpoint inhibitors. P-selectin glycoprotein ligand-1 (PSGL-1), recently identified as a promoter of T cell exhaustion in melanoma murine models, has emerged as a novel immune checkpoint protein and promising immunotherapeutic target. In this study, we investigated the potential of PSGL-1 antibody targeting in B-cell lymphoma. Using allogeneic coculture systems, we demonstrated that targeted antibody interventions against human PSGL-1 resulted in enhancement of T cell activation and effector cytokine production in response to lymphoma cells. Moreover, in vitro treatment of primary lymphoma cell suspensions with PSGL-1 antibody resulted in increased activation of autologous lymphoma-infiltrating T cells. Finally, using a syngeneic B-cell lymphoma mouse model, we found that PSGL-1 antibody treatment significantly slowed tumor development and reduced endpoint tumor burden. This anti-tumoral action was accompanied by augmented tumor infiltration with CD4+ and CD8+ T cells and reduced infiltration with regulatory T cells. These results demonstrate that PSGL-1 antibody blockade bolsters T-cell activity against B-cell lymphoma, suggesting a potential novel immunotherapeutic approach to treat these malignancies.