Khazaie Khashayarsha, von Boehmer Harald
Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Boston, MA 02115, USA.
Semin Cancer Biol. 2006 Apr;16(2):124-36. doi: 10.1016/j.semcancer.2005.11.006. Epub 2006 Jan 26.
There is sufficient evidence to suggest that tumor growth elicits specific immune responses, including CD8(+) and CD4(+) T cell responses that may delay tumor growth and could potentially be harnessed to eradicate cancer. Nevertheless the frequent outcome of cancer is lethality associated with uncontrolled growth and dissemination of tumor cells. The failure of the immune response may be naturally programmed and related to a specific subpopulation of CD4(+)CD25(+) regulatory T cells, whose function is to protect us against autoimmunity. Recent investigations have shed light on the in vivo behavior and functions of these cells. It is becoming evident that a major impact of these cells is on the cytolytic action of specific CD8(+) T cells that target the tumor. Inhibition of cytotoxicity is dependent on TGF-beta signaling by the effector cells. Thus, targeting immune regulation may provide a promising approach to the immune therapy of cancer. This approach however could also have unexpected deleterious consequences, as surprising new observations indicate that regulatory T cells can also delay tumor growth by independent mechanisms that relate to their cross talk with the innate immune response to cancer.
有充分证据表明肿瘤生长会引发特异性免疫反应，包括CD8(+)和CD4(+) T细胞反应，这些反应可能会延缓肿瘤生长，并有可能被用于根除癌症。然而，癌症常见的结局是与肿瘤细胞不受控制的生长和扩散相关的致死性。免疫反应的失败可能是自然编程的，并且与CD4(+)CD25(+)调节性T细胞的特定亚群有关，其功能是保护我们免受自身免疫的影响。最近的研究揭示了这些细胞在体内的行为和功能。越来越明显的是，这些细胞的主要影响在于靶向肿瘤的特异性CD8(+) T细胞的细胞溶解作用。细胞毒性的抑制依赖于效应细胞的TGF-β信号传导。因此，靶向免疫调节可能为癌症免疫治疗提供一种有前景的方法。然而，这种方法也可能产生意想不到的有害后果，因为令人惊讶的新观察结果表明，调节性T细胞也可以通过与其与癌症先天免疫反应的相互作用相关的独立机制来延缓肿瘤生长。
