Cellular Immune Responses for Squamous Cell Carcinoma Antigen Recognized by T Cells 3 in Patients with Hepatocellular Carcinoma.
Cellular Immune Responses for Squamous Cell Carcinoma Antigen Recognized by T Cells 3 in Patients with Hepatocellular Carcinoma.
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T细胞3识别肝细胞癌患者识别的鳞状细胞癌抗原的细胞免疫反应。
DOI：
10.1371/journal.pone.0170291
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Kaneko S
中科院分区：
文献类型：
--
作者：
Kaji K;Mizukoshi E;Yamashita T;Arai K;Sunagozaka H;Fushimi K;Nakagawa H;Yamada K;Terashima T;Kitahara M;Kaneko S
T细胞识别的鳞状细胞癌抗原3（SART 3）是在许多癌症中表达的肿瘤相关抗原，在肿瘤排斥中起作用。在这项研究中，我们研究了其作为肝细胞癌（HCC）免疫靶点的有用性。应用免疫荧光和免疫组化方法检测SART 3在肝癌细胞系和肝癌组织中的表达。两种源自SART 3的肽（SART 3109和SART 3315）用于免疫学分析。采用干扰素-γ（IFN-γ）酶联免疫斑点法和细胞毒性T淋巴细胞（CTL）试验检测了47例HCC患者外周血单个核细胞（PBMC）和8例HCC患者肿瘤浸润淋巴细胞的T细胞应答。通过在12名HCC患者中接种SART 3109研究了使用SART 3衍生肽的免疫治疗的安全性（试验注册号：UMIN 000005677）。免疫荧光和免疫组化分析表明，SART 3表达在6个肝癌细胞系，并在肝癌组织中，包括甲胎蛋白阴性的个人。通过用肽刺激PBMC产生SART 3特异性CTL，并且它们显示出对表达该蛋白的HCC细胞的细胞毒性。在47例HCC患者中，分别有25.5%和10.6%的患者对SART 3109和SART 3315表现出显著应答。证实SART 3109特异性产生IFN-γ的CTL浸润到肿瘤部位。在疫苗接种研究中，没有观察到严重的不良事件，并且在五名受试患者中的四名中新诱导了肽特异性CTL。SART 3是一种免疫抑制剂候选物，并且来自该抗原的肽可用于HCC免疫治疗。UMIN000005677
Squamous cell carcinoma antigen recognized by T cells 3 (SART3), a tumor-associated antigen expressed in many cancers, functions in tumor rejection. In this study, we investigated its usefulness as an immunotherapeutic target in hepatocellular carcinoma (HCC). The expression of SART3 in hepatoma cell lines and HCC tissues was investigated by immunofluorescence and immunohistochemical analyses. Two peptides derived from SART3 (SART3109 and SART3315) were used for immunological analysis. T-cell responses were investigated by interferon-gamma (IFN-γ) enzyme-linked immunospot and cytotoxic T lymphocyte (CTL) assays using peripheral blood mononuclear cells (PBMCs) in 47 patients, and tumor-infiltrating lymphocytes in 8 of 47 patients with HCC. The safety of immunotherapy using a SART3-derived peptide was investigated by vaccinations of SART3109 in 12 patients with HCC (trial registration: UMIN000005677). The immunofluorescence and immunohistochemical analyses showed that SART3 was expressed in six HCC cell lines, and in HCC tissues including of alpha-fetoprotein-negative individuals. SART3-specific CTLs were generated by stimulating PBMCs with the peptides, and they showed cytotoxicity against HCC cells expressing the protein. Of the 47 HCC patients, 25.5% and 10.6% showed significant responses to SART3109 and SART3315, respectively. The infiltration of SART3109-specific IFN-γ-producing CTLs into the tumor site was confirmed. In the vaccination study, no severe adverse events were observed, and the peptide-specific CTLs were newly induced in four of five patients tested. SART3 is an immunotherapeutic candidate, and peptides from this antigen may be applied in HCC immunotherapy. UMIN000005677