PSGL-1/SIGLEC-5 and CD39/CD73 axes are dysregulated in obstructive sleep apnea

<bold>Introduction:</bold> A higher incidence of cancer represents a major burden for obstructive sleep apnea (OSA) patients. Increasing evidence supports the role of intermittent hypoxia (IH) in dampening immune surveillance, thus facilitating tumor development. However, the mechanisms driving this process remain to be completely understood. Here, we explore the expression of two immune checkpoint axis PSGL-1/SIGLEC-5 and CD39/CD73, analyzing its relation with OSA severity and assessing the role of IH. <bold>Methods:</bold> 166 OSA patients and 83 control subjects were prospectively recruited. The expression of PSGL-1/SIGLEC-5 and CD39/CD73 was assessed by flow cytometry. <italic>In vitro</italic> models were used to explore the role of IH. CD39 and CD73 soluble forms were measured in plasma (sCD39 and sCD73), along with adenosine. Finally, <italic>ex vivo</italic> models were used to assess PSGL-1 impact on T-cell function and to analyze leucocyte capability to release sCD39 and sCD73. <bold>Results:</bold> PSGL-1, SIGLEC-5, and CD39 expression is upregulated while CD73 is downregulated in the leucocytes from severe OSA patients. In addition, sCD39 and sCD73 are upregulated in OSA plasma. Furthermore, <italic>in vitro</italic> data suggest that IH mediates the upregulation of PSGL-1, SIGLEC-5, CD39, and CD73. Interestingly, <italic>ex vivo</italic> results suggest CD73 downregulation could be mediated by a higher release of sCD73 by OSA T-lymphocytes. Finally, alterations in CD39/CD73 axis may underlie the upsurge of the immune suppressive agent adenosine in the plasma of OSA patients. Meanwhile, PSGL-1 plays an inhibitory role in T-cell proliferation capacity. <bold>Conclusion:</bold> CD39/CD73 and PSGL-1/SIGLEC-5 might constitute additional axes contributing to the disruption of immune surveillance in OSA patients.