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

  • Leukemia. 2025 Jan;39(1):178-188. doi: 10.1038/s41375-024-02446-w.
João L Pereira  1  2  3 ,  Liliana Arede  1 ,  Francisca Ferreira  1  2  4 ,  Andreia Matos  1  5  6  7  8 ,  Dulcineia Pereira  1  2  9 ,  Rita F Santos  1  10  11 ,  Alexandre M Carmo  1  10 ,  Maria J Oliveira  1  3  5 ,  José C Machado  1  2  3 ,  Delfim Duarte  1  3  9 ,  Nuno R Dos Santos  12  13
Affiliations
  • 1. i3S-Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal.
  • 2. IPATIMUP-Institute of Molecular Pathology and Immunology, University of Porto, Porto, Portugal.
  • 3. Faculty of Medicine, University of Porto, Porto, Portugal.
  • 4. Master´s Program in Bioengineering, ICBAS-Instituto de Ciências Biomédicas Abel Salazar, and Faculty of Engineering, University of Porto, Porto, Portugal.
  • 5. INEB-Instituto de Engenharia Biomédica, Universidade do Porto, Porto, Portugal.
  • 6. ICBAS-Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal.
  • 7. Genetics Laboratory, Faculty of Medicine, University of Lisbon, Lisboa, Portugal.
  • 8. Ecogenetics and Human Health, Environmental Health Institute, Faculty of Medicine, University of Lisbon, Lisboa, Portugal.
  • 9. Department of Hematology and Bone Marrow Transplantation, IPO Porto, Porto, Portugal.
  • 10. IBMC-Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal.
  • 11. ESS-IPP, School of Health, Polytechnic of Porto, Porto, Portugal.
  • 12. i3S-Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal. [email protected].
  • 13. IPATIMUP-Institute of Molecular Pathology and Immunology, University of Porto, Porto, Portugal. [email protected].
PMID: 39455852 DOI: 10.1038/s41375-024-02446-w
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 murine Melanoma 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 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, anti-PSGL-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.