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癌-睾丸抗原OY-TES-1在肝细胞癌中的表达及免疫原性

Cancer-testis Antigen OY-TES-1 Expression and Immunogenicity in Hepatocellular Carcinoma.

作者信息

Luo Bin, Yun Xiang, Li Jing, Fan Rong, Guo Wen-Wen, Liu Chang, Lin Yong-da, Ge Ying-Ying, Zeng Xia, Bi Shui-Qing, Nong Wei-Xia, Zhang Qing-Mei, Xie Xiao-Xun

机构信息

School of Basic Medical Sciences, Guangxi Medical University, Nanning, 530021, China.

Department of Surgery, the First Affiliated Hospital, Guangxi Medical University, Nanning, 530021, China.

出版信息

Curr Med Sci. 2020 Aug;40(4):719-728. doi: 10.1007/s11596-020-2241-x. Epub 2020 Aug 29.

Abstract

Cancer testis (CT) antigens have received particular attention in cancer immunotherapy. OY-TES-1 is a member of CT antigens. This study was to evaluate OY-TES-1 expression and immunogenicity in hepatocelluar carcinoma (HCC). OY-TES-1 mRNA expression was detected in 56 HCC tissues and 5 normal liver tissues by reverse transcriptase PCR (RT-PCR). Of the 56 cases of HCC tissues tested, 37 cases had tumor and matched adjacent non-cancer tissues and were subjected to both RT-PCR and quantitative real-time PCR. OY-TES-1 protein was subsequently observed on a panel of tissue microarrays. Sera from patients were tested for OY-TES-1 antibody by ELISA. To identify OY-TES-1 capable of inducing cellular immune response, OY-TES-1 protein was used to sensitize dentritic cells and the cytotoxicity effect was measured in vitro. The results showed that OY-TES-1 mRNA was highly expressed in 41 of the 56 (73.21%) HCC tissues, whereas none in 5 normal liver tissues. OY-TES-1 mRNA was frequently expressed not only in HCC tissues (72.97%, 27/37), but also in paired adjacent non-cancer tissues (64.86%, 24/37). But the mean expression level of OY-TES-1 mRNA in HCC tissues was significantly higher than that in adjacent non-cancer tissues (0.76854 vs. 0.09834, P=0.021). Immunohistochemistry showed that OY-TES-1 protein expression was detected in 6 of the 49 cases of HCC tissues, and absent in 9 cases of normal liver and 6 cases of cirrhosis tissues. Seropositivity was detected in 10 of the 45 HCC patients, but not detected in 17 cirrhosis patients and 76 healthy donors. The specific cytotoxic T cells elicited by OY-TES-1 could kill HLA-A HCC cell line which expressed OY-TES-1. The target lysis was mainly HLA class I -dependent and could be blocked by antibodies against monomorphic HLA class I but not HLA class II molecule. In summary, OY-TES-1 expression is up-regulated in HCC tissues and can be recognized by humoral and cellular responses, which suggests that OY-TES-1 is an attractive target for tumor immunotherapy in HCC.

摘要

癌睾丸(CT)抗原在癌症免疫治疗中受到了特别关注。OY-TES-1是CT抗原家族的一员。本研究旨在评估OY-TES-1在肝细胞癌(HCC)中的表达及免疫原性。采用逆转录聚合酶链反应(RT-PCR)检测56例HCC组织和5例正常肝组织中OY-TES-1 mRNA的表达。在检测的56例HCC组织中,37例有肿瘤组织及配对的癌旁非癌组织,对其进行RT-PCR和实时定量PCR检测。随后在一组组织芯片上观察OY-TES-1蛋白。采用酶联免疫吸附测定(ELISA)检测患者血清中的OY-TES-1抗体。为鉴定能够诱导细胞免疫反应的OY-TES-1,用OY-TES-1蛋白致敏树突状细胞,并在体外检测其细胞毒性作用。结果显示,56例HCC组织中有41例(73.21%)OY-TES-1 mRNA高表达,而5例正常肝组织中均未表达。OY-TES-1 mRNA不仅在HCC组织中频繁表达(72.97%,27/37),在配对的癌旁非癌组织中也有表达(64.86%,24/37)。但HCC组织中OY-TES-1 mRNA的平均表达水平显著高于癌旁非癌组织(0.76854 vs. 0.09834,P=0.021)。免疫组织化学显示,49例HCC组织中有6例检测到OY-TES-1蛋白表达,9例正常肝组织和6例肝硬化组织中均未检测到。45例HCC患者中有10例血清呈阳性,17例肝硬化患者和76例健康供者中均未检测到。OY-TES-1诱导产生的特异性细胞毒性T细胞可杀伤表达OY-TES-1的HLA-A HCC细胞系。靶细胞裂解主要依赖HLA-I类分子,可被抗单态性HLA-I类分子抗体阻断,而不能被抗HLA-II类分子抗体阻断。综上所述,OY-TES-1在HCC组织中表达上调,可被体液免疫和细胞免疫识别,提示OY-TES-1是HCC肿瘤免疫治疗的一个有吸引力的靶点。

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