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

• Type: Article in International Scientific Journal
• Date: 2024

Authors

Pereira, JL (Author) Other; Arede, L (Author) Other; Ferreira, F (Author) Other; Matos, A (Author) Other; Pereira, D (Author) Other; Santos, RF (Author) Other; Carmo, AM (Author) Other; Oliveira, MJ (Author) Other; Machado JC (Author) FMUP; Duarte, D (Author) Other; dos Santos, NR (Author) Other

Journal

Title: Leukemia

ISSN: 0887-6924

Publisher: Springer Nature

Indexing

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Other information

Authenticus ID: P-010-NS3

DOI: 10.1038/s41375-024-02446-w

Abstract (EN): 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 E mu-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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 11