Savage Peter A, Leventhal Daniel S, Malchow Sven
Department of Pathology, University of Chicago, Chicago, IL, USA.
Immunol Rev. 2014 May;259(1):245-58. doi: 10.1111/imr.12166.
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.
许多肿瘤表达的抗原能够被T淋巴细胞特异性或选择性地识别，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环境中演变，防止正常组织发生自身免疫攻击的免疫机制同时也在限制抗肿瘤免疫。特别是，清除自身反应性T细胞以及免疫抑制性调节性T细胞（Tregs）的产生被认为是阻碍抗肿瘤免疫反应的主要障碍。在此，我们讨论了目前对于肿瘤浸润性T细胞群体所识别的抗原、塑造这些细胞库的机制以及转录因子自身免疫调节因子（Aire）在这些过程中的作用的理解。进一步阐明这些原理对于优化新兴的癌症免疫疗法以及合理设计具有强大抗肿瘤活性且毒性有限的新型疗法可能至关重要。
