VEGF-A modulates expression of inhibitory checkpoints on CD8+ T cells in tumors.
VEGF-A modulates expression of inhibitory checkpoints on CD8+ T cells in tumors.
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DOI：
10.1084/jem.20140559
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发表时间：
2015-02-09
期刊：
影响因子：
--
通讯作者：
Terme M
中科院分区：
文献类型：
--
作者：
Voron T;Colussi O;Marcheteau E;Pernot S;Nizard M;Pointet AL;Latreche S;Bergaya S;Benhamouda N;Tanchot C;Stockmann C;Combe P;Berger A;Zinzindohoue F;Yagita H;Tartour E;Taieb J;Terme M
肿瘤微环境中的VEGF-A产生增强了PD-1和其他与CD 8 + T细胞耗竭相关的抑制性检查点的表达，这可以用抗VEGF/VEGFR治疗逆转。免疫逃逸是肿瘤发生的先决条件。为了避开免疫系统，肿瘤发展出不同的机制，包括T细胞耗竭，其特征在于免疫抑制受体（如PD-1、CTLA-4、Tim-3）的表达和功能的进行性丧失。靶向PD-1和CTLA-4的疗法的最新发展引起了极大的兴趣，因为它们在患有晚期转移性肿瘤的患者中诱导了持久的客观反应。然而，PD-1表达的调节，从而耗竭，是不清楚的。VEGF-A是一种由肿瘤产生的促血管生成分子，在免疫抑制微环境的形成中起着关键作用。我们在目前的工作中报告，在肿瘤微环境中产生的VEGF-A增强了PD-1和其他参与CD 8 + T细胞耗竭的抑制性检查点的表达，这可以通过靶向VEGF-A-VEGFR的抗血管生成剂逆转。鉴于这些结果，抗血管生成分子与抑制性检查点的免疫调节剂的结合可能在产生VEGF-A的肿瘤中特别令人感兴趣。
VEGF-A production in the tumor microenvironment enhances expression of PD-1 and other inhibitory checkpoints involved with CD8+ T cell exhaustion, which can be reversed with anti-VEGF/VEGFR treatment. Immune escape is a prerequisite for tumor development. To avoid the immune system, tumors develop different mechanisms, including T cell exhaustion, which is characterized by expression of immune inhibitory receptors, such as PD-1, CTLA-4, Tim-3, and a progressive loss of function. The recent development of therapies targeting PD-1 and CTLA-4 have raised great interest since they induced long-lasting objective responses in patients suffering from advanced metastatic tumors. However, the regulation of PD-1 expression, and thereby of exhaustion, is unclear. VEGF-A, a proangiogenic molecule produced by the tumors, plays a key role in the development of an immunosuppressive microenvironment. We report in the present work that VEGF-A produced in the tumor microenvironment enhances expression of PD-1 and other inhibitory checkpoints involved in CD8+ T cell exhaustion, which could be reverted by anti-angiogenic agents targeting VEGF-A–VEGFR. In view of these results, association of anti-angiogenic molecules with immunomodulators of inhibitory checkpoints may be of particular interest in VEGF-A-producing tumors.
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影响因子：
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Johnson, Randall S.
影响因子：
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作者：
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影响因子：
30.5
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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.20100643
发表时间：
2010-09-27
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Sakuishi K;Apetoh L;Sullivan JM;Blazar BR;Kuchroo VK;Anderson AC
通讯作者：
Anderson AC