Yamaguchi Tomoyuki, Sakaguchi Shimon
Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, 53 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
Semin Cancer Biol. 2006 Apr;16(2):115-23. doi: 10.1016/j.semcancer.2005.11.005. Epub 2006 Jan 11.
Naturally occurring CD25(+)CD4(+) regulatory T cells (T(R) cells), which specifically express the transcription factor Foxp3, engage in the maintenance of immunological self-tolerance and suppressive control of aberrant or excessive immune responses to foreign antigens. They may, on the other hand, impede immune surveillance against cancer and hamper the development of effective immunity to autologous tumor cells. Indeed, natural T(R) cells have been observed to predominantly infiltrate tumor masses especially in the early phase of tumor progression. Depletion of natural T(R) cells by removing CD25(+) T cells prior to tumor challenge is therefore able to provoke effective tumor immunity in animals. Furthermore, attenuation of T(R) cell-mediated suppression in on-going anti-tumor immune responses, for example by altering signaling through CTLA-4 or GITR expressed by natural T(R) cells, can enhance the responses and thereby eradicate advanced cancers. A combination of depletion or attenuation of T(R) cells and concomitant stimulation of effector T cells, systemically or locally in tumors, may be a feasible immunotherapy for cancer.
天然存在的CD25(+)CD4(+)调节性T细胞（T(R)细胞）特异性表达转录因子Foxp3，参与维持免疫自身耐受性，并对针对外来抗原的异常或过度免疫反应进行抑制性控制。另一方面，它们可能会阻碍针对癌症的免疫监视，并妨碍对自体肿瘤细胞产生有效的免疫反应。事实上，已观察到天然T(R)细胞主要浸润肿瘤块，尤其是在肿瘤进展的早期阶段。因此，在肿瘤攻击前通过去除CD25(+)T细胞来消耗天然T(R)细胞，能够在动物体内激发有效的肿瘤免疫。此外，在正在进行的抗肿瘤免疫反应中，减弱T(R)细胞介导的抑制作用，例如通过改变天然T(R)细胞表达的CTLA-4或GITR的信号传导，可以增强反应，从而根除晚期癌症。在肿瘤中全身或局部消耗或减弱T(R)细胞并同时刺激效应T细胞，可能是一种可行的癌症免疫疗法。
