D'Atri S, Romani L, Bonmassar E, Grohmann U, Tricarico M, Christmas S E, Moore M
Istituto Dermopatico dell'Immacolata (IDI), Rome, Italy.
Int J Immunopharmacol. 1994 Jul;16(7):569-79. doi: 10.1016/0192-0561(94)90108-2.
Murine tumor cells treated with triazene compounds (TZC), in vivo or in vitro, are capable of eliciting specific transplantation resistance in syngeneic hosts, and T-cell-mediated proliferative and cytotoxic responses, directed against novel drug-induced antigen(s). Since this phenomenon, referred to as chemical xenogenization (CX) could open up new perspectives in the immunochemotherapy of human neoplasias, it was of interest to investigate whether CX could also occur in human tumors. However, established human tumor cell lines along with fully immunocompetent autologous lymphocytes, are seldom available. Therefore studies were carried out to test whether parental or TZC-treated tumor cells could be differentially recognized by allogeneic lymphocytes. Experiments were performed in both human and murine models, using a lung adenocarcinoma line treated in vitro with TZC, or an established xenogenized mouse lymphoma, respectively. The results indicate that allogeneic cytotoxic T-lymphocytes (CTL) recognize specifically murine TZC-treated tumor cells. This was supported by the finding that antisera directed against the drug-treated cells abrogated the generation and the cytolytic activity of allogeneic CTL reactive against the TZC-treated tumor. In addition it was found that changes of the antigenic pattern of cell membrane recognizable by cloned allogeneic CTL occur in the TZC-treated human carcinoma cell line.
用三氮烯化合物(TZC)处理的小鼠肿瘤细胞,无论在体内还是体外,都能够在同基因宿主中引发特异性移植抗性,以及针对新型药物诱导抗原的T细胞介导的增殖和细胞毒性反应。由于这种被称为化学异种源化(CX)的现象可能为人类肿瘤的免疫化学疗法开辟新的前景,因此研究CX是否也会在人类肿瘤中发生具有重要意义。然而,建立的人类肿瘤细胞系以及具有完全免疫活性的自体淋巴细胞很少能够获得。因此,开展了研究以测试亲代或经TZC处理的肿瘤细胞是否能被同种异体淋巴细胞差异识别。分别使用体外经TZC处理的肺腺癌细胞系或已建立的异种源化小鼠淋巴瘤,在人类和小鼠模型中进行了实验。结果表明,同种异体细胞毒性T淋巴细胞(CTL)能特异性识别经TZC处理的小鼠肿瘤细胞。针对药物处理细胞的抗血清消除了针对经TZC处理肿瘤的同种异体CTL的产生和细胞溶解活性,这一发现支持了上述结论。此外,还发现经TZC处理的人类癌细胞系中,可被克隆的同种异体CTL识别的细胞膜抗原模式发生了变化。