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

Area of Science:

• Immunology
• Sleep Medicine
• Oncology

Background:

• Obstructive sleep apnea (OSA) is associated with a higher incidence of cancer, but the underlying molecular mechanisms remain unclear.
• P-selectin glycoprotein-1 (PSGL-1), an adhesion receptor, has emerged as a potential immune checkpoint relevant to cancer therapy.

Purpose of the Study:

• To investigate the role of PSGL-1 and its ligands (VISTA, SIGLEC-5) in OSA patients.
• To explore the impact of intermittent hypoxia (IH) on PSGL-1 expression and T-cell function in OSA.

Main Methods:

• Assessed PSGL-1 and ligand expression in leukocytes from OSA patients and controls using in vitro and ex vivo models.
• Evaluated the effect of IH on PSGL-1 expression and T-cell function.

Main Results:

• PSGL-1 expression was upregulated in T-lymphocytes of severe OSA patients, linked to intermittent hypoxia.
• PSGL-1 demonstrated an inhibitory effect on T-cell proliferation.
• SIGLEC-5 expression increased in monocytes from OSA patients, suggesting IH regulatory role.

Conclusions:

• PSGL-1 may function as an immune checkpoint, contributing to T-cell dysfunction in OSA.
• This dysfunction disrupts immune surveillance, potentially explaining increased cancer incidence and aggressiveness in OSA patients.