Nie Yongzhan, Wu Kaichun, Yang Jinghua, Tian Fengqi, Li Ling, Chen Baojun, Fan Daiming
Institute of Digestive Diseases, Xijing Hospital, Xi'an, China.
J Immunother. 2003 Sep-Oct;26(5):403-11. doi: 10.1097/00002371-200309000-00003.
Tumor-specific cytotoxic T lymphocytes (CTLs) from patients with early-stage tumors are usually more efficient at attacking tumor cells than CTLs from the progressing tumor stages. The authors investigated the antitumor activity of CTLs from gastric cancer patents and healthy donors. In this study, peripheral blood lymphocytes (PBLs) from gastric cancer patients and healthy donors were stimulated with HLA-A matched allogeneic gastric cancer cells such as KATO-3, MKN45, and SGC7901. Three different populations of lymphocyte, p5-CTL-KATO, h4-CTL-MKN45, and h4-CTL-KATO, were induced and expanded. Flow cytometry analyses showed that 85.2% to 97.8% of these cells were CD3-positive and 45.5% to 51.2% were CD8-positive. The induced CTLs efficiently kill HLA-A2 or HLA-A24 gastric cancer cells through CTL-mediated cytotoxicity. However, no effects were observed for other cancer cells or HLA-A2 negative gastric cancer cells. The specific cytotoxicity of the induced CTLs was further confirmed by cold-target inhibition and monoclonal antibody blockage. These results suggest that CTL-mediated cytotoxicity specific for tumor cells can be produced by stimulating PBLs from healthy donors using HLA-A matched tumor cells, which will lead to the development of new immunotherapeutic strategies to kill cancer cells.
早期肿瘤患者的肿瘤特异性细胞毒性T淋巴细胞（CTL）通常比进展期肿瘤阶段的CTL更有效地攻击肿瘤细胞。作者研究了来自胃癌患者和健康供体的CTL的抗肿瘤活性。在本研究中，用HLA - A匹配的同种异体胃癌细胞如KATO - 3、MKN45和SGC7901刺激来自胃癌患者和健康供体的外周血淋巴细胞（PBL）。诱导并扩增了三种不同的淋巴细胞群体，p5 - CTL - KATO、h4 - CTL - MKN45和h4 - CTL - KATO。流式细胞术分析表明，这些细胞中85.2%至97.8%为CD3阳性，45.5%至51.2%为CD8阳性。诱导的CTL通过CTL介导的细胞毒性有效杀伤HLA - A2或HLA - A24胃癌细胞。然而，对其他癌细胞或HLA - A2阴性胃癌细胞未观察到作用。通过冷靶抑制和单克隆抗体阻断进一步证实了诱导的CTL的特异性细胞毒性。这些结果表明，使用HLA - A匹配的肿瘤细胞刺激健康供体的PBL可以产生针对肿瘤细胞的CTL介导的细胞毒性，这将导致开发新的免疫治疗策略来杀死癌细胞。
