Hypoxemia-induced TIGIT expression in obstructive sleep apnea is reversible with continuous positive airway pressure

TL;DR

This study shows that low oxygen levels in sleep apnea increase TIGIT, an immune checkpoint, and that this effect can be reversed with CPAP treatment.

Contribution

The study demonstrates that TIGIT expression in OSA is reversible with CPAP and linked to hypoxemia via HIF-1α.

Findings

TIGIT expression on T cells is elevated in OSA patients and correlates with hypoxemia indicators.

In vitro hypoxemia models confirm HIF-1α's role in upregulating TIGIT expression.

One year of CPAP treatment significantly reduces TIGIT expression in OSA patients.

Abstract

Obstructive Sleep Apnea (OSA) is a prevalent syndrome characterized by intermittent hypoxemia and elevated risk of comorbidities, including cancer. In this context, the immune response may contribute to tumor evasion though immune checkpoints. Herein, we investigate the TIGIT immune checkpoint in OSA patients and its association with hypoxemia.

We recruited 94 severe OSA patients without cancer evidence and 92 control subjects to study the TIGIT receptors and their ligands in T cells and monocytes, respectively. Furthermore, we examined the role of hypoxemia – particularly the involvement of HIF-1α (hypoxia inducible factor-1α) - using a combination of in vitro models. Moreover, we evaluated the effect of one year of standard therapy with CPAP (continuous positive airway pressure) in OSA patients.

Our data suggests that the TIGIT expression increase on T cells from OSA patients and is associated with clinical indicators of hypoxemia. In vitro hypoxemia models confirm the role of HIF-1α in the upregulation of TIGIT expression. However, within the OSA cohort without evidence of cancer, we did not detect significant differences in TIGIT ligands, either in their membrane-bound or soluble forms. Importantly, one year of CPAP treatment reduce the TIGIT expression.

Hypoxemia in OSA patients increases TIGIT expression, contributing to a T-cell exhaustion phenotype. CPAP treatment reduces TIGIT expression on T lymphocytes. Altogether, these findings highlight the impact of hypoxemia effect on immune response, which may help explain the high cancer incidence in OSA patients.

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