Pan Xue, Zhong Anyuan, Xing Yufei, Shi Minhua, Qian Bin, Zhou Tong, Chen Yongjing, Zhang Xueguang
Department of Respiration, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, P.R. China.
Department of Immunology, Medical College of Soochow University, Suzhou, Jiangsu 215006, P.R. China; Key Laboratory of Infection and Immunity, Soochow University, Suzhou, Jiangsu 200241, P.R. China.
Exp Ther Med. 2016 Oct;12(4):2161-2168. doi: 10.3892/etm.2016.3611. Epub 2016 Aug 23.
Soluble and membrane-bound programmed death ligand-1 (sPD-L1 and mPD-L1, respectively) have been demonstrated to participate in the immune suppression of non-small cell lung cancer. However, the contribution of sPD-L1 and mPD-L1 to immune regulation and disease progression in patients with pleural effusions remains unknown. The present study evaluated the levels of sPD-L1 and membrane-bound PD-1/PD-L1 in the peripheral blood and pleural effusions of patients with tuberculous pleural effusion (TPE), malignant pleural effusion (MPE) and non-tuberculous non-malignant pleural effusion (n-TB n-M). Furthermore, selected T lymphocytes and cluster of differentiation (CD)14 monocytes were co-cultured to investigate the potential effect of the PD-1/PD-L1 pathway in TPE. Levels of sPD-L1 and PD-L1 on CD14 monocytes were increased in the TPE group, as compared with the MPE and n-TB n-M groups. Furthermore, sPD-L1 levels and the expression levels of PD-L1 on CD14 monocytes were demonstrated to be positively correlated with interferon (IFN)-γ concentration in pleural effusions. Therefore, IFN-γ may increase the expression of PD-L1 on CD14 monocytes . Cell counting kit-8 analysis demonstrated that anti-PD-L1 antibody was able to partially reverse the proliferation of T lymphocytes in the co-culture system. The results of the present study indicated that sPD-L1 or mPD-L1 are associated with the immune regulation and disease progression of TPE, and may serve as possible biomarkers of TPE. Furthermore, sPD-L1 and the PD-1/PD-L1 pathway of TPE may be associated with the Th1 immune response; therefore, an anti-PD-1/PD-L1 pathway suggests a potential immune therapy strategy for the treatment of TPE.
可溶性和膜结合型程序性死亡配体1（分别为sPD-L1和mPD-L1）已被证明参与非小细胞肺癌的免疫抑制。然而，sPD-L1和mPD-L1对胸腔积液患者免疫调节和疾病进展的作用仍不清楚。本研究评估了结核性胸腔积液（TPE）、恶性胸腔积液（MPE）和非结核非恶性胸腔积液（n-TB n-M）患者外周血和胸腔积液中sPD-L1以及膜结合型PD-1/PD-L1的水平。此外，将选择的T淋巴细胞和分化簇（CD）14单核细胞进行共培养，以研究PD-1/PD-L1通路在TPE中的潜在作用。与MPE组和n-TB n-M组相比，TPE组CD14单核细胞上sPD-L1和PD-L1的水平升高。此外，sPD-L1水平以及CD14单核细胞上PD-L1的表达水平被证明与胸腔积液中干扰素（IFN）-γ浓度呈正相关。因此，IFN-γ可能增加CD14单核细胞上PD-L1的表达。细胞计数试剂盒-8分析表明，抗PD-L1抗体能够部分逆转共培养系统中T淋巴细胞的增殖。本研究结果表明，sPD-L1或mPD-L1与TPE的免疫调节和疾病进展相关，可能作为TPE的潜在生物标志物。此外，TPE的sPD-L1和PD-1/PD-L1通路可能与Th1免疫反应相关；因此，抗PD-1/PD-L1通路提示了一种治疗TPE的潜在免疫治疗策略。
