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肺鳞状细胞癌患者中CD14⁺ HLA-DR⁺ 髓源性抑制细胞的功能分析

Functional analysis of CD14HLA-DR myeloid-derived suppressor cells in patients with lung squamous cell carcinoma.

作者信息

Chen Yun, Pan Guichang, Tian Dongbo, Zhang Yifei, Li Taoping

机构信息

Department of Sleep Medicine Center, NanFang Hospital of Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.

Department of Respiration, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan, Guangdong 511500, P.R. China.

出版信息

Oncol Lett. 2017 Jul;14(1):349-354. doi: 10.3892/ol.2017.6146. Epub 2017 May 10.

Abstract

Immunomodulatory therapy is a potential effective treatment for advanced cancer that may provide an alternative to chemotherapy, which patients can experience adverse side effects to. Myeloid-derived suppressor cells (MDSCs) have been demonstrated to cause T-cell tolerance in rodents and humans; however, little is known about the role of MDSCs in squamous cell carcinoma. In the present study, the role of MDSCs in lung squamous cell carcinoma was investigated. Peripheral blood from 78 patients with lung squamous cell carcinoma and 30 healthy controls was examined for the presence and function of human MDSCs, denoted as monocyte differentiation antigen CD14-positive HLA class II histocompatibility antigen DR-negative/low (CD14 HLA-DR) cells by flow cytometry. The sorted T-cell surface glyoprotein CD3 (CD3) cells and CD14HLA-DR cells were subsequently co-cultured with a tumor cell line (NCI-H226). T-cell apoptosis was detected using annexin-V-fluorescein isothicyanate and 7-aminoactinomycin D. Interferon-γ (IFN-γ) levels were detected using an ELISA. The frequency of MDSCs in the peripheral blood mononuclear cells (PBMCs) from patients with lung squamous cell carcinoma was significantly higher compared with that of the healthy controls (P<0.05), whereas the frequency of T-cell surface glyoprotein CD4 (CD4) T cells and CD8 T cells in PBMCs was significantly decreased (P<0.05). In an MDSC/CD8 co-culture system, the proportion of CD8 T-cell apoptosis significantly increased with the increase in ratio of MDSCs (P<0.05), while the proportion of tumor cell apoptosis significantly decreased (P<0.05). The concentration of IFN-γ significantly decreased with the increase in MDSCs (P<0.05). Therefore, MDSCs participate in the immune escape of lung squamous cell carcinoma, and may provide a possible therapeutic strategy for the treatment of this disease.

摘要

免疫调节疗法是一种针对晚期癌症的潜在有效治疗方法,它可能为化疗提供一种替代方案,因为患者可能会经历化疗的不良副作用。髓源性抑制细胞(MDSCs)已被证明会导致啮齿动物和人类的T细胞耐受;然而,关于MDSCs在鳞状细胞癌中的作用知之甚少。在本研究中,研究了MDSCs在肺鳞状细胞癌中的作用。通过流式细胞术检测了78例肺鳞状细胞癌患者和30例健康对照者外周血中人类MDSCs的存在和功能,将其表示为单核细胞分化抗原CD14阳性、HLA II类组织相容性抗原DR阴性/低(CD14 HLA-DR)细胞。随后将分选的T细胞表面糖蛋白CD3(CD3)细胞和CD14HLA-DR细胞与肿瘤细胞系(NCI-H226)共培养。使用膜联蛋白-V-异硫氰酸荧光素和7-氨基放线菌素D检测T细胞凋亡。使用酶联免疫吸附测定法检测干扰素-γ(IFN-γ)水平。与健康对照者相比,肺鳞状细胞癌患者外周血单个核细胞(PBMCs)中MDSCs的频率显著更高(P<0.05),而PBMCs中T细胞表面糖蛋白CD4(CD4)T细胞和CD8 T细胞的频率显著降低(P<0.05)。在MDSC/CD8共培养系统中,随着MDSCs比例的增加,CD8 T细胞凋亡比例显著增加(P<0.05),而肿瘤细胞凋亡比例显著降低(P<0.05)。随着MDSCs的增加,IFN-γ浓度显著降低(P<0.05)。因此,MDSCs参与肺鳞状细胞癌的免疫逃逸,并可能为该疾病的治疗提供一种可能的治疗策略。

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