Obstructive sleep apnoea (OSA) is associated with higher cancer incidence, tumour aggressiveness and cancer mortality, as well as greater severity of infections, which have been attributed to an immune deregulation. We studied the expression of programmed cell death (PD)-1 receptor and its ligand (PD-L1) on immune cells from patients with OSA, and its consequences on immune-suppressing activity. We report that PD-L1 was overexpressed on monocytes and PD-1 was overexpressed on CD8+ T-cells in a severity-dependent manner. PD-L1 and PD-1 overexpression were induced in both the human in vitro and murine models of intermittent hypoxia, as well as by hypoxia-inducible factor-1α transfection. PD-L1/PD-1 crosstalk suppressed T-cell proliferation and activation of autologous T-lymphocytes and impaired the cytotoxic activity of CD8+ T-cells. In addition, monocytes from patients with OSA exhibited high levels of retinoic acid related orphan receptor, which might explain the differentiation of myeloid-derived suppressor cells. Intermittent hypoxia upregulated the PD-L1/PD-1 crosstalk in patients with OSA, resulting in a reduction in CD8+ T-cell activation and cytotoxicity, providing biological plausibility to the increased incidence and aggressiveness of cancer and the higher risk of infections described in these patients. PD-L1/PD-1 crosstalk is upregulated in obstructive sleep apnoea patients and immunomodulates T-cell response http://ow.ly/gBEx30dZ7dd

中文翻译：

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缺氧诱导的 PD-L1/PD-1 串扰损害睡眠呼吸暂停中的 T 细胞功能

阻塞性睡眠呼吸暂停 (OSA) 与更高的癌症发病率、肿瘤侵袭性和癌症死亡率以及更严重的感染有关，这归因于免疫失调。我们研究了程序性细胞死亡 (PD)-1 受体及其配体 (PD-L1) 在 OSA 患者免疫细胞上的表达，及其对免疫抑制活性的影响。我们报告 PD-L1 在单核细胞上过度表达，PD-1 在 CD8+ T 细胞上以严重程度依赖的方式过度表达。PD-L1 和 PD-1 过表达在间歇性缺氧的人体外模型和鼠模型以及缺氧诱导因子 1α 转染中均被诱导。PD-L1/PD-1 串扰抑制了 T 细胞增殖和自体 T 淋巴细胞的活化，并削弱了 CD8+ T 细胞的细胞毒活性。此外，OSA 患者的单核细胞表现出高水平的视黄酸相关孤儿受体，这可能解释了髓源性抑制细胞的分化。间歇性缺氧上调 OSA 患者的 PD-L1/PD-1 串扰，导致 CD8+ T 细胞活化和细胞毒性降低，为癌症发病率和侵袭性增加以及这些中描述的更高感染风险提供生物学合理性耐心。PD-L1/PD-1 串扰在阻塞性睡眠呼吸暂停患者中上调并免疫调节 T 细胞反应 http://ow.ly/gBEx30dZ7dd 导致 CD8+ T 细胞活化和细胞毒性降低，为癌症发病率和侵袭性增加以及这些患者中描述的更高感染风险提供生物学合理性。PD-L1/PD-1 串扰在阻塞性睡眠呼吸暂停患者中上调并免疫调节 T 细胞反应 http://ow.ly/gBEx30dZ7dd 导致 CD8+ T 细胞活化和细胞毒性降低，为癌症发病率和侵袭性增加以及这些患者中描述的更高感染风险提供生物学合理性。PD-L1/PD-1 串扰在阻塞性睡眠呼吸暂停患者中上调并免疫调节 T 细胞反应 http://ow.ly/gBEx30dZ7dd