Antitumor Activity and Some Immunological Properties of γδ T-Cells from Patients with Gastrointestinal Carcinomas
Antitumor Activity and Some Immunological Properties of γδ T-Cells from Patients with Gastrointestinal Carcinomas
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发表时间：
2008-09
影响因子：
2
通讯作者：
M. Murayama;Yoshimasa Tanaka;J. Yagi;T. Uchiyama;K. Ogawa
中科院分区：
文献类型：
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作者：
M. Murayama;Yoshimasa Tanaka;J. Yagi;T. Uchiyama;K. Ogawa
目的：表达 Vgamma2Jgamma1.2Vdelta2-TCR 的人 γδ T 细胞以不依赖 MHC 的方式识别微生物焦磷酸单酯，并对多种肿瘤细胞发挥细胞毒活性。在本研究中，对来自胃肠道癌患者的 γδ T 细胞的免疫学特性进行了检查，并将其与来自健康成人个体的γδ T 细胞进行比较，旨在开发一种使用非肽抗原 2-甲基-3-丁烯基-1-焦磷酸 (2M3B1PP) 刺激的γδ T 细胞的新型癌症免疫疗法。材料和方法：从胃肠道癌患者中获得外周血单核细胞（PBM）和肿瘤相关淋巴细胞（TAL）。用 2M3B1PP 刺激单核细胞 2 周，并检查扩增的 γδ T 细胞在 T 细胞受体 (TCR) 接合时产生的细胞因子以及针对同种异体肿瘤和自体肿瘤细胞的细胞毒活性。为了进行比较，使用 2M3B1PP 类似地刺激源自健康成年志愿者的 PBMC，并分析所得的 γδ T 细胞的效应功能。结果：胃肠道癌患者的所有外周血和肿瘤相关的 γδ T 细胞制剂在 2M3B1PP 的作用下均出现剧烈增殖，达到与健康供体相当的水平。当用 CD3 单克隆抗体攻击时，癌症患者来源的 γδ T 细胞分泌大量炎症细胞因子 IFN-γ，并对同种异体肿瘤细胞系以及自体肿瘤细胞表现出有效的细胞毒活性。结论：源自胃肠道癌患者的外周血和肿瘤相关 γδT 细胞与健康个体的免疫活性相同，可用于胃肠道恶性肿瘤的新型癌症免疫疗法。
OBJECTIVES: Human gammadelta T-cells expressing Vgamma2Jgamma1.2Vdelta2-TCR recognize microbial pyrophosphomonoesters in an MHC-independent manner and exert cytotoxic activity on a wide variety of tumor cells. In the present study, the immunological properties of gammadelta T-cells derived from patients with gastrointestinal carcinomas were examined and compared with those from healthy adult individuals, aiming to develop a novel cancer immunotherapy using gammadelta T-cells stimulated with one of the nonpeptide antigens, 2-methyl-3-butenyl-1-pyrophosphate (2M3B1PP). MATERIALS AND METHODS: Peripheral blood mononuclear cells (PBMs) and tumor-associated lymphocytes (TAL) were obtained from patients with gastrointestinal carcinomas. The mononuclear cells were stimulated with 2M3B1PP for 2 weeks and the expanded gammadelta T cells were examined for cytokine production upon T-cell receptor (TCR) engagement and cytotoxic activity against allogeneic tumors and autologous tumor cells. For comparison, PBMCs derived from healthy adult volunteers were similarly stimulated with 2M3B1PP and the resulting gammadelta T-cells were analyzed for effector functions. RESULTS: All the peripheral blood- and tumor-associated gammadelta T-cell preparations from patients with gastrointestinal carcinomas proliferated vigorously in response to 2M3B1PP to comparable levels to those from healthy donors. When challenged with CD3 monoclonal antibodies, the carcinoma patient-derived gammadelta T-cells secreted a large amount of inflammatory cytokine, IFN-gamma, and exhibited a potent cytotoxic activity against allogeneic tumor cell lines as well as autologous tumor cells. CONCLUSION: Both peripheral blood- and tumor-associated gammadelta T-cells derived from patients with gastrointestinal carcinomas were as immunologically active as those from healthy individuals and could be utilized for a novel cancer immunotherapy for gastrointestinal malignancies.