CD40 and CD70 co-stimulate a potent in vivo antitumor T cell response
CD40 and CD70 co-stimulate a potent in vivo antitumor T cell response
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DOI：
10.1097/00002371-199805000-00009
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发表时间：
1998-05-01
影响因子：
3.9
通讯作者：
Kruisbeek, AM
中科院分区：
文献类型：
--
作者：
Nieland, JD;Graus, YF;Kruisbeek, AM
在多项研究中，CD80（一种有效的共刺激分子）据报道负责通过 CD80 转染的肿瘤细胞诱导 CD8（+）抗肿瘤 T 细胞反应。然而，肿瘤表达 CD80 并不总能确保产生 T 细胞介导的抗肿瘤反应。肿瘤固有的免疫原性及其主要组织相容性复合物 (MHC) 表达状态等变量会影响该方法的功效。因此，在这项研究中，研究了另外两种共刺激配体 CD40 和 CD70 共刺激抗肿瘤反应的能力。将 CD40 和 CD70 的功效与 CD80 的功效进行比较，包括体外 CD4 和 CD8 T 细胞共刺激能力及其诱导体内抗肿瘤反应的能力。此外，还测试了 CD40 和 CD70 在体内诱导长期记忆反应的能力，这通过诱导肿瘤特异性细胞毒性 T 淋巴细胞 (CTL) 和排斥野生型肿瘤细胞来定义。研究发现，尽管 CD40 主要刺激 CD4 T 细胞，但转染 CD40 的 MHC II 类阴性 P815 肿瘤细胞变得具有高度免疫原性，并在体内诱导持久记忆肿瘤特异性 CTL。此外，CD40 和 CD70 成为 CD80 的强大甚至更好的替代品，可改善体内肿瘤免疫原性。虽然其作用机制仍有待确定，但这些发现提出了免疫治疗的其他策略。
In several studies, CD80, a potent co-stimulatory molecule, has been reported to be responsible for the induction of CD8(+) antitumor T cell responses by CD80-transfected tumor cells. However, expression of CD80 by tumors not always ensures generation of a T cell-mediated antitumor response. Variables such as the inherent immunogenicity of a tumor and its major histocompatibility complex (MHC) expression status affect the efficacy of this approach. Therefore, in this study two other co-stimulatory ligands, CD40 and CD70, have been investigated for their ability to co-stimulate antitumor responses. The efficacy of CD40 and CD70 is compared with that of CD80, with respect to CD4 and CD8 T cell co-stimulatory capacity in vitro and their ability to induce in vivo antitumor responses. Furthermore, CD40 and CD70 are tested for their capacity to induce a long-lived memory response in vivo, as defined both by induction of tumor-specific cytotoxic T lymphocytes (CTLs) and rejection of wild-type tumor cells. It was found that, despite the fact that CD40 predominantly stimulates CD4 T cells, CD40-transfected MHC class II-negative P815 tumor cells become highly immunogenic and induce long-lasting memory tumor-specific CTLs in vivo. Furthermore, CD40 and CD70 emerge as powerful and even superior alternatives to CD80 for improving tumor immunogenicity in vivo. While the mechanisms by which they do so remain to be defined, these findings suggest additional strategies for immunotherapy.