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
School of Basic Medical Sciences, Guangxi Medical University, Nanning, 530021, China.
Department of Surgery, the First Affiliated Hospital, Guangxi Medical University, Nanning, 530021, China.
Curr Med Sci. 2020 Aug;40(4):719-728. doi: 10.1007/s11596-020-2241-x. Epub 2020 Aug 29.
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.
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。
