Targeting Tim-3 and PD-1 pathways to reverse T cell exhaustion and restore anti-tumor immunity.
Targeting Tim-3 and PD-1 pathways to reverse T cell exhaustion and restore anti-tumor immunity.
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DOI：
10.1084/jem.20100643
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发表时间：
2010-09-27
期刊：
影响因子：
--
通讯作者：
Anderson AC
中科院分区：
文献类型：
--
作者：
Sakuishi K;Apetoh L;Sullivan JM;Blazar BR;Kuchroo VK;Anderson AC
免疫应答在避免癌症中起着重要作用;然而，免疫抑制机制阻碍了有效的抗肿瘤免疫。荷瘤宿主中的T细胞功能障碍或耗竭是这样一种机制。PD-1已被鉴定为慢性疾病状态中耗尽的T细胞的标志物，并且PD-1-PD-1 L相互作用的阻断已显示部分恢复T细胞功能。我们已经发现，T细胞免疫球蛋白粘蛋白（Tim）3表达的CD 8+肿瘤浸润淋巴细胞（TILs）在荷实体瘤小鼠。所有Tim-3+ TIL共表达PD-1，Tim-3+PD-1+ TIL代表浸润肿瘤的T细胞的主要部分。Tim-3+PD-1+ TIL表现出最严重的耗竭表型，如通过不能增殖和产生IL-2、TNF和IFN-γ所定义的。我们进一步发现，Tim-3和PD-1通路的联合靶向在控制肿瘤生长方面比单独靶向任一通路更有效。
The immune response plays an important role in staving off cancer; however, mechanisms of immunosuppression hinder productive anti-tumor immunity. T cell dysfunction or exhaustion in tumor-bearing hosts is one such mechanism. PD-1 has been identified as a marker of exhausted T cells in chronic disease states, and blockade of PD-1–PD-1L interactions has been shown to partially restore T cell function. We have found that T cell immunoglobulin mucin (Tim) 3 is expressed on CD8+ tumor-infiltrating lymphocytes (TILs) in mice bearing solid tumors. All Tim-3+ TILs coexpress PD-1, and Tim-3+PD-1+ TILs represent the predominant fraction of T cells infiltrating tumors. Tim-3+PD-1+ TILs exhibit the most severe exhausted phenotype as defined by failure to proliferate and produce IL-2, TNF, and IFN-γ. We further find that combined targeting of the Tim-3 and PD-1 pathways is more effective in controlling tumor growth than targeting either pathway alone.
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影响因子：
5.4
作者：
Urbani, Simona;Amadei, Barbara;Ferrari, Carlo
通讯作者：
Ferrari, Carlo
影响因子：
30.5
作者：
Latchman, Y;Wood, CR;Freeman, GJ
通讯作者：
Freeman, GJ
影响因子：
5.4
作者：
Wherry, EJ;Blattman, JN;Ahmed, R
通讯作者：
Ahmed, R
影响因子：
30.5
作者：
Blackburn, Shawn D.;Shin, Haina;Haining, W. Nicholas;Zou, Tao;Workman, Creg J.;Polley, Antonio;Betts, Michael R.;Freeman, Gordon J.;Vignali, Dario A. A.;Wherry, E. John
通讯作者：
Wherry, E. John
DOI：
10.1084/jem.20061496
发表时间：
2006-10-02
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Petrovas C;Casazza JP;Brenchley JM;Price DA;Gostick E;Adams WC;Precopio ML;Schacker T;Roederer M;Douek DC;Koup RA
通讯作者：
Koup RA