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

2025-01Artigo de investigação Acesso aberto
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dc.contributor.authorPereira, João L.
dc.contributor.authorArede, Liliana
dc.contributor.authorFerreira, Francisca
dc.contributor.authorMatos, Andreia
dc.contributor.authorPereira, Dulcineia
dc.contributor.authorSantos, Rita F.
dc.contributor.authorCarmo, Alexandre M.
dc.contributor.authorOliveira, Maria J.
dc.contributor.authorMachado, José C.
dc.contributor.authorDuarte, Delfim
dc.contributor.authorSantos, Nuno R. dos
dc.contributor.authorSantos, Ana Rita
dc.date.accessioned2026-01-14T11:48:36Z
dc.date.available2026-01-14T11:48:36Z
dc.date.issued2025-01
dc.description.abstractDespite 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.eng
dc.identifier.citationPereira, 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-w
dc.identifier.doi10.1038/s41375-024-02446-w
dc.identifier.eissn1476-5551
dc.identifier.issn0887-6924
dc.identifier.urihttp://hdl.handle.net/10400.22/31506
dc.language.isoeng
dc.peerreviewedyes
dc.publisherSpringer Nature
dc.relation.hasversionhttps://www.nature.com/articles/s41375-024-02446-w
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectPSGL-1
dc.subjectB-cell lymphoma
dc.subjectCD4+ and CD8+ T cells
dc.titleAntibody blockade of the PSGL-1 immune checkpoint enhances T-cell responses to B-cell lymphomaeng
dc.typeresearch article
dspace.entity.typePublication
oaire.citation.endPage188
oaire.citation.startPage178
oaire.citation.titleLeukemia
oaire.citation.volume39
oaire.versionhttp://purl.org/coar/version/c_970fb48d4fbd8a85
person.familyNameSantos
person.givenNameAna Rita
person.identifier.ciencia-id0911-4138-0C3A
person.identifier.orcid0000-0003-0139-0285
relation.isAuthorOfPublicationd71931b8-d869-4334-993c-ba14ad713f01
relation.isAuthorOfPublication.latestForDiscoveryd71931b8-d869-4334-993c-ba14ad713f01

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