Pereira, João L.Arede, LilianaFerreira, FranciscaMatos, AndreiaPereira, DulcineiaSantos, Rita F.Carmo, Alexandre M.Oliveira, Maria J.Machado, José C.Duarte, DelfimSantos, Nuno R. dosSantos, Ana Rita2026-01-142026-01-142025-01Pereira, J. L., Arede, L., Ferreira, F., Matos, A., Pereira, D., Santos, R. F., Carmo, A. M., Oliveira, M. J., Machado, J. C., Duarte, D., & dos Santos, N. R. (2025). Antibody blockade of the PSGL-1 immune checkpoint enhances T-cell responses to B-cell lymphoma. Leukemia, 39(1), 178–188. https://doi.org/10.1038/s41375-024-02446-w0887-6924http://hdl.handle.net/10400.22/31506Despite 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 murine melanoma models, has emerged as a novel immune checkpoint protein and promising immunotherapeutic target. In this study, we investigated the potential of PSGL1 antibody targeting in B-cell lymphoma. Using allogeneic co-culture systems, we demonstrated that targeted antibody interventions against human PSGL-1 enhanced 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. Using the A20 syngeneic B-cell lymphoma mouse model, we found that PSGL-1 antibody treatment significantly slowed tumor development and reduced the endpoint tumor burden. This antitumoral effect was accompanied by augmented tumor infiltration of CD4+ and CD8+ T cells and reduced infiltration of regulatory T cells. Finally, antiPSGL-1 administration enhanced the expansion of CAR T cells previously transferred to mice bearing the aggressive Eμ-Myc lymphoma cells and improved disease control. These results demonstrate that PSGL-1 antibody blockade bolsters T-cell activity against B-cell lymphoma, suggesting a potential novel immunotherapeutic approach for treating these malignancies.engPSGL-1B-cell lymphomaCD4+ and CD8+ T cellsresearch article10.1038/s41375-024-02446-w1476-5551