Fast-tracked CTL: Rapid induction of potent anti-tumor killer T cells in situ (Retracted Article)
Fast-tracked CTL: Rapid induction of potent anti-tumor killer T cells in situ (Retracted Article)
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DOI：
10.1002/eji.200637002
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发表时间：
2007-07-01
影响因子：
5.4
通讯作者：
Pease, Larry R.
中科院分区：
文献类型：
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作者：
Heckman, Karin L.;Schenk, Erin L.;Pease, Larry R.
目前引发对肿瘤相关或过表达的自身抗原特异性的溶细胞T细胞应答的策略依赖于多次免疫和体外扩增方案。在这里，我们报告了在用IgM免疫调节剂B7-DC XAb治疗后仅6天，体内诱导活化的肿瘤特异性CD 8（+）CTL。在肿瘤攻击时对小鼠的抗体处理引发了有效的CTL，其特异性区分MHC相容性肿瘤。值得注意的是，这些效应细胞不是由幼稚CTL前体的广泛增殖产生的，尽管它们的诱导需要CD 4（+）T细胞的帮助和经典的B7共刺激信号。肿瘤靶点被识别并在细胞内裂解。MHC限制性穿孔素依赖性方式，表明这些快速诱导的效应子类似于传统定义的CTL，尽管发现没有引起效应子/记忆标志物CD 44和活化标志物CD 69表达的强烈增加。这些CTL在具有良好建立的肿瘤的动物中诱导，并导致抗肿瘤保护，强调了这种类型的效应T细胞群在癌症患者中的治疗潜力。
Current strategies to elicit cytolytic T cell responses specific for tumor- associated or over-expressed self antigens rely on multiple immunizations and in vitro expansion schemes. Here we report the in vivo induction of activated tumor-specific CD8(+) CTL just 6 days after treatment with the IgM immune modulator B7-DC XAb. Antibody treatment of mice at the time of tumor challenge elicited potent CTL with a specificity that distinguished between MHC-compatible tumors. Remarkably, these effector cells were not generated by the extensive proliferation of naive CTL precursors, though their induction required CD4(+) T cell help and classical B7 costimulatory signals. Tumor targets were recognized and lysed in an. MHC-restricted, perforin-dependent manner, indicating that these rapidly induced effectors resemble traditionally defined CTL, despite the finding that strong increases in the expression of the effector/memory marker CD44 and the activation marker CD69 were not elicited. These CTL were induced in animals bearing well-established tumors and resulted in anti-tumor protection, underscoring the therapeutic potential of this type of effector T cell population in cancer patients.