Ligation of the OX40 co-stimulatory receptor reverses self-Ag and tumor-induced CD8 T-cell anergy in vivo.
Ligation of the OX40 co-stimulatory receptor reverses self-Ag and tumor-induced CD8 T-cell anergy in vivo.
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DOI：
10.1002/eji.200939348
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发表时间：
2009-08
影响因子：
5.4
通讯作者：
Weinberg, Andrew D.
中科院分区：
文献类型：
--
作者：
Redmond, William L.;Gough, Michael J.;Weinberg, Andrew D.
肿瘤特异性CD8 T细胞外周耐受通过克隆缺失、抑制和诱导无反应性发生，并可限制抗肿瘤免疫的产生。几个研究小组已经证明，前列腺癌可以使肿瘤特异性CD8 T细胞无反应性，这表明逆转肿瘤诱导的无反应性可以大大增强抗肿瘤免疫力。最近的研究表明，通过TNFR超家族成员OX40（CD134）共刺激受体的信号传导可以增强CD4和CD8 T细胞的扩增、分化和记忆细胞的产生。然而，OX40连接是否可以逆转CD8 T细胞无反应性，更具体地说，肿瘤诱导的CD8 T细胞无反应性，仍然不清楚。在目前的研究中，我们证明了OX40连接可以逆转非肿瘤宿主中CD8 T细胞对前列腺特异性自身抗原的无能。此外，OX40参与逆转了肿瘤特异性CD8 T细胞的无反应性，并恢复了肿瘤反应性CD8 T细胞的增殖能力，这减弱了肿瘤生长并提高了荷瘤宿主的存活率。这些数据表明，OX40连接可以挽救无反应性自身或肿瘤反应性CD8 T细胞在体内的功能，并表明OX40介导的治疗可以提供一种新的手段，通过恢复以前无反应性的肿瘤特异性CD8 T细胞的反应性，提高抗肿瘤免疫力。
Tumor-specific CD8 T cell peripheral tolerance occurs through clonal deletion, suppression, and the induction of anergy and can limit the generation of anti-tumor immunity. Several groups have demonstrated that prostate cancer can render tumor-specific CD8 T cells anergic, suggesting reversing tumor-induced anergy may greatly augment anti-tumor immunity. Recent work has demonstrated that signaling through the OX40 (CD134) co-stimulatory receptor, a member of the TNFR super-family, can augment CD4 and CD8 T cell expansion, differentiation, and the generation of memory cells. However, whether OX40 ligation can reverse CD8 T cell anergy, and more specifically, tumor-induced CD8 T cell anergy, remains unclear. In the current study, we demonstrate that OX40 ligation can reverse CD8 T cell anergy to a prostate-specific self-antigen in non-tumor bearing hosts. Furthermore, OX40 engagement reversed tumor-specific CD8 T cell anergy and restored the proliferative capacity of tumor-reactive CD8 T cells, which attenuated tumor growth and enhanced the survival of tumor-bearing hosts. These data demonstrate that OX40 ligation can rescue the function of anergic self or tumor-reactive CD8 T cells in vivo and suggests that OX40-mediated therapy may provide a novel means of boosting anti-tumor immunity by restoring the responsiveness of previously anergic tumor-specific CD8 T cells.
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OX40触发调节性T细胞抑制块并促进肿瘤排斥。
影响因子：
15.3
作者：
Piconese, Silvia;Valzasina, Barbara;Colombo, Mario P.
通讯作者：
Colombo, Mario P.
DOI：
10.1084/jem.187.2.225
发表时间：
1998-01-19
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Khoruts A;Mondino A;Pape KA;Reiner SL;Jenkins MK
通讯作者：
Jenkins MK
影响因子：
4.4
作者：
Gramaglia, I;Jember, A;Croft, M
通讯作者：
Croft, M
影响因子：
20.3
作者：
Biagi, E;Dotti, G;Brenner, M
通讯作者：
Brenner, M
影响因子：
15.9
作者：
Horai, R;Nakajima, A;Iwakura, Y
通讯作者：
Iwakura, Y