Frontiers in Immunology (Oct 2023)

PSGL-1: a novel immune checkpoint driving T-cell dysfunction in obstructive sleep apnea

  • Elena Díaz-García,
  • Elena Díaz-García,
  • Aldara García-Sánchez,
  • Aldara García-Sánchez,
  • Enrique Alfaro,
  • Enrique Alfaro,
  • Cristina López-Fernández,
  • Cristina López-Fernández,
  • Eva Mañas,
  • Irene Cano-Pumarega,
  • Eduardo López-Collazo,
  • Eduardo López-Collazo,
  • Francisco García-Río,
  • Francisco García-Río,
  • Francisco García-Río,
  • Carolina Cubillos-Zapata,
  • Carolina Cubillos-Zapata

DOI
https://doi.org/10.3389/fimmu.2023.1277551
Journal volume & issue
Vol. 14

Abstract

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IntroductionAlthough higher incidence of cancer represents a major burden for obstructive sleep apnea (OSA) patients, the molecular pathways driving this association are not completely understood. Recently, the adhesion receptor P-selectin glycoprotein-1 (PSGL 1) has been identified as a novel immune checkpoint, which are recognized major hallmarks in several types of cancer and have revolutionized cancer therapy.MethodsThe expression of PSGL-1 and its ligands VISTA and SIGLEC-5 was assessed in the leucocytes of OSA patients and control subjects exploring the role of intermittent hypoxia (IH) using in vitro models. In addition, PSGL-1 impact on T-cells function was evaluated by ex vivo models.ResultsData showed PSGL-1 expression is upregulated in the T-lymphocytes from patients with severe OSA, indicating a relevant role of hypoxemia mediated by intermittent hypoxia. Besides, results suggest an inhibitory role of PSGL-1 on T-cell proliferation capacity. Finally, the expression of SIGLEC-5 but not VISTA was increased in monocytes from OSA patients, suggesting a regulatory role of intermittent hypoxia.DiscussionIn conclusion, PSGL-1 might constitute an additional immune checkpoint leading to T-cell dysfunction in OSA patients, contributing to the disruption of immune surveillance, which might provide biological plausibility to the higher incidence and aggressiveness of several tumors in these patients.

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