Redistribution of Monocyte Subsets in Obstructive Sleep Apnea Syndrome Patients Leads to an Imbalanced PD-1/PD-L1 Cross-Talk with CD4/CD8 T Cells

Abstract

Obstructive sleep apnea syndrome (OSAS) represents a substantial disease of recurrent sleep fragmentation, leading to intermittent hypoxia and subsequent diseases such as cardiovascular, metabolic, or cognitive dysfunctions. In addition, OSAS is considered as low-grade systemic inflammation, which is associated with a higher incidence of cancer, severity of infections, and an overall immune dysregulation. This research project aims to comprehensively investigate the interplay of wholesome sleep and the immune functions of circulating monocytes and T cells in OSAS patients, which are known to be affected by oxidative stress. We studied the distribution of the CD14/CD16 characterized monocyte subsets in peripheral blood as well as their PD-L1 expression and complex formation with T cells. Furthermore, a detailed analysis of T cell subsets with regard to their PD-1 and PD-L1 expression was performed. Data revealed a decrease of classical monocytes accompanied by an increase of both CD16 + monocyte subsets in OSAS patients that was positively correlated with the body mass index. OSAS patients revealed an increased PD-1 and PD-L1 expression in T cells and monocytes, respectively, which was linked to the severity of monocyte subset alterations. The complex formation of monocytes and T cells was also elevated in OSAS patients, which indicates a deregulated PD-1/PD-L1 cross-talk between these cells. Our data show for the first time, to our knowledge, massive alterations of peripheral monocyte subsets in response to OSAS and its accompanying phenomena.

Reconstitution of Monocyte Subsets and PD-L1 Expression but Not T Cell PD-1 Expression in Obstructive Sleep Apnea Patients upon PAP Therapy

“…Most patients ( n = 18) revealed a moderate decrease in classical monocytes accompanied by an increase in intermediate monocytes. Seven patients showed a severe drop in classical monocytes with a strong increase in intermediate and non-classical monocytes in comparison to healthy donors [ 14 ]. The monocyte subset distribution was not correlated to the BMI or AHI of the patients.…”

“…Flow cytometry data revealed a significant increase in classical monocytes accompanied by a drop in intermediate and non-classical subsets in all analyzed patients ( Figure 1 ). Most of the patients even revealed monocyte distributions comparable to healthy donors in response to PAP [ 14 ].…”

“…We have recently shown that OSA patients reveal decreased levels of CD14 ++ CD16 − classical monocytes accompanied by an increase in both CD16 + monocyte subsets and an imbalanced PD-1/PD-L1 cross-talk with CD4/CD8 T cells. [ 14 ].…”

Clinical outcomes and influencing factors of PD‑1/PD‑L1 in hepatocellular carcinoma (Review)

“…Nivolumab and pembrolizaumab have been brought into guidelines due to their exact efficacy (11). PD-1 and PD-L1 expression, biomarkers of inflammation, inflammatory genes, AR and EGFR signaling have clear evidence of the impact on PD-1/PD-L1 clinical outcomes (47)(48)(49)(50)(51)(52)(53)(54)(55). The reason why cemiplimab, atezolizumab, avelumab, durvalumab have not been included in the guidelines for the treatment of HCC is that their efficacy and safety is not completely certain, and several trials are still ongoing (29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40).…”

“…Markers of systemic inflammation, such as elevated neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio and α-fetoprotein are associated with poor prognosis in HCC (40). Recent evidence suggest that when cells gradually evolve into malignant tumors, PD-L1 expression increases and the interaction between PD-1 and PD-L1 inhibits the self-reactive T cells, resulting in the over balance of PD-L1, PD-L2 and PD-1 (49). It has been demonstrated that androgen (AR) receptor can inhibit PD-L1 expression in HCC cells, and AR transcriptionally represses PD-L1 by binding to its promoter.…”