A2aR antagonists: Next generation checkpoint blockade for cancer immunotherapy.
A2aR antagonists: Next generation checkpoint blockade for cancer immunotherapy.
复制标题
A2aR 拮抗剂：用于癌症免疫治疗的下一代检查点阻断。
DOI：
10.1016/j.csbj.2015.03.008
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发表时间：
2015
影响因子：
6
通讯作者：
Powell, Jonathan D.
中科院分区：
文献类型：
--
作者：
Leone, Robert D.;Lo, Ying-Chun;Powell, Jonathan D.
最近几年，在癌症治疗的免疫疗法的发展方面取得了令人兴奋的进展。这在很大程度上是由于所谓检查站封锁的发展。也就是说，阻断抑制性受体如CTLA-4和PD-1的抗体，从而释放针对肿瘤的抗原特异性免疫应答。很明显，肿瘤通过篡夺在负调节正常免疫应答中起作用的途径来逃避免疫应答。在这方面，免疫微环境中导致A2 a受体活化的腺苷已被证明代表一种这样的负反馈回路。实际上，肿瘤微环境具有相对高浓度的腺苷。为此，阻断A2 a受体活化具有显著增强小鼠模型中的抗肿瘤免疫的潜力。本综述将展示A2 a受体阻断剂增强肿瘤疫苗、检查点阻断剂和过继性T细胞治疗的能力。此外，由于最近的几项研究表明，在某些条件下A2 a受体阻断可以促进肿瘤进展，我们还将探索腺苷信号传导在免疫反应中的复杂性。尽管A2 a受体途径的重要细微差别需要进一步阐明，但迄今为止的研究强烈支持开发A2 a受体拮抗剂（其中一些已经在帕金森病的III期临床试验中进行了测试）作为免疫治疗设备中的新模式。
The last several years have witnessed exciting progress in the development of immunotherapy for the treatment of cancer. This has been due in great part to the development of so-called checkpoint blockade. That is, antibodies that block inhibitory receptors such as CTLA-4 and PD-1 and thus unleash antigen-specific immune responses against tumors. It is clear that tumors evade the immune response by usurping pathways that play a role in negatively regulating normal immune responses. In this regard, adenosine in the immune microenvironment leading to the activation of the A2a receptor has been shown to represent one such negative feedback loop. Indeed, the tumor microenvironment has relatively high concentrations of adenosine. To this end, blocking A2a receptor activation has the potential to markedly enhance anti-tumor immunity in mouse models. This review will present data demonstrating the ability of A2a receptor blockade to enhance tumor vaccines, checkpoint blockade and adoptive T cell therapy. Also, as several recent studies have demonstrated that under certain conditions A2a receptor blockade can enhance tumor progression, we will also explore the complexities of adenosine signaling in the immune response. Despite important nuances to the A2a receptor pathway that require further elucidation, studies to date strongly support the development of A2a receptor antagonists (some of which have already been tested in phase III clinical trials for Parkinson Disease) as novel modalities in the immunotherapy armamentarium.
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影响因子：
--
作者：
Gao ZW;Dong K;Zhang HZ
通讯作者：
Zhang HZ
影响因子：
--
作者：
Fishman, P;Bar-Yehuda, S;Synowitz, M;Powell, J D;Klotz, K N;Gessi, S;Borea, P A
通讯作者：
Borea, P A
影响因子：
11.2
作者：
Cekic C;Day YJ;Sag D;Linden J
通讯作者：
Linden J
影响因子：
11.2
作者：
Cekic C;Linden J
通讯作者：
Linden J
DOI：
10.1056/nejmoa1200694
发表时间：
2012-06-28
期刊：
The New England journal of medicine
影响因子：
--
作者：
Brahmer JR;Tykodi SS;Chow LQ;Hwu WJ;Topalian SL;Hwu P;Drake CG;Camacho LH;Kauh J;Odunsi K;Pitot HC;Hamid O;Bhatia S;Martins R;Eaton K;Chen S;Salay TM;Alaparthy S;Grosso JF;Korman AJ;Parker SM;Agrawal S;Goldberg SM;Pardoll DM;Gupta A;Wigginton JM
通讯作者：
Wigginton JM