Shaping the repertoire of tumor-infiltrating effector and regulatory T cells.

Shaping the repertoire of tumor-infiltrating effector and regulatory T cells.
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DOI:
10.1111/imr.12166
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发表时间:
2014-05
影响因子:
8.7
通讯作者:
Malchow S
Malchow S
中科院分区:
医学1区
文献类型:
--
作者:
Savage PA;Leventhal DS;Malchow S

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许多肿瘤表达可被T淋巴细胞特异性或选择性识别的抗原,这表明T细胞介导的免疫可用于癌症的免疫治疗。然而,由于肿瘤起源于正常细胞并在自身组织的背景下进化,因此防止正常组织的自身免疫攻击的免疫机制平行地发挥作用以限制抗肿瘤免疫。特别是,自身反应性T细胞的清除和免疫抑制性调节性T细胞(Tcells)的发展被认为是阻碍抗肿瘤免疫应答的主要障碍。在这里,我们讨论了目前的理解有关肿瘤浸润性T细胞群,形成这些细胞的剧目的机制,以及在这些过程中的转录因子自身免疫调节因子(Aire)的作用所识别的抗原。这些原则的进一步阐明对于优化新兴的癌症免疫疗法以及合理设计表现出稳健的抗肿瘤活性和有限毒性的新型疗法可能是至关重要的。
Many tumors express antigens that can be specifically or selectively recognized by T lymphocytes, suggesting that T cell-mediated immunity may be harnessed for the immunotherapy of cancer. However, since tumors originate from normal cells and evolve within the context of self tissues, the immune mechanisms that prevent the autoimmune attack of normal tissues function in parallel to restrict anti-tumor immunity. In particular, the purging of autoreactive T cells and the development of immune-suppressive regulatory T cells (Tregs) are thought to be major barriers impeding anti-tumor immune responses. Here, we discuss current understanding regarding the antigens recognized by tumor-infiltrating T cell populations, the mechanisms that shape the repertoire of these cells, and the role of the transcription factor autoimmune regulator (Aire) in these processes. Further elucidation of these principles is likely to be critical for optimizing emerging cancer immunotherapies, and for the rational design of novel therapies exhibiting robust anti-tumor activity with limited toxicity.
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