Cancer-testis Antigen OY-TES-1 Expression and Immunogenicity in Hepatocellular Carcinoma
Cancer-testis Antigen OY-TES-1 Expression and Immunogenicity in Hepatocellular Carcinoma
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肝细胞癌中癌睾丸抗原OY-TES-1的表达及免疫原性
DOI：
10.1007/s11596-020-2241-x
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发表时间：
2020-08-01
影响因子：
2.4
通讯作者：
Xie, Xiao-xun
中科院分区：
文献类型：
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作者：
Luo, Bin;Yun, Xiang;Xie, Xiao-xun
癌症睾丸（CT）抗原在癌症免疫治疗中受到特别关注。OY-TES-1是CT抗原的成员。本研究旨在探讨OY-TES-1在肝细胞癌（HCC）中的表达及其免疫原性。应用逆转录聚合酶链反应（RT-PCR）检测56例肝癌组织和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例有肿瘤且匹配的邻近非癌组织，并进行RT-PCR和定量实时PCR。随后在一组组织微阵列上观察OY-TES-1蛋白。用ELISA法检测患者血清中OY-TES-1抗体。为鉴定OY-TES-1蛋白是否具有诱导细胞免疫应答的作用，用OY-TES-1蛋白致敏树突状细胞，体外检测其细胞毒作用，结果表明：OY-TES-1 mRNA在56例肝癌组织中有41例（73.21%）高表达，而在5例正常肝组织中无表达。OY-TES-1 mRNA在肝癌组织中的表达率为72.97%（27/37），在癌旁组织中的表达率为64.86%（24/37）。但OY-TES-1 mRNA在肝癌组织中的平均表达水平显著高于癌旁组织（0.76854vs.0.09834，P=0.021）。免疫组化结果显示，OY-TES-1蛋白在49例肝癌组织中有6例阳性表达，9例正常肝组织和6例肝硬化组织中均无表达。45例HCC患者中有10例检测到血清学阳性，而17例肝硬化患者和76例健康供体中未检测到血清学阳性。OY-TES-1诱导的特异性细胞毒T细胞对表达OY-TES-1的HLA-A2+肝癌细胞株具有杀伤作用。靶溶解主要是HLA I类依赖性的，并且可以被抗单形HLA I类分子的抗体阻断，但不能被抗HLA II类分子的抗体阻断。综上所述，OY-TES-1在HCC组织中表达上调，并且可以被体液和细胞应答识别，这表明OY-TES-1是HCC中肿瘤免疫治疗的有吸引力的靶点。
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 measuredin 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 (0.76854vs.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-A2+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.