University of Salford, School of Environment and Life Sciences, Centre for Biochemistry, Drug Design and Cancer Research, Salford, UK.
Expert Opin Biol Ther. 2010 Nov;10(11):1573-86. doi: 10.1517/14712598.2010.529126.
The active suppression of immune responses against tumor is a major barrier to the likely success of cancer immunotherapy. There is now compelling evidence implicating T regulatory cells (Tregs) as being key players driving immune suppression. Elevated frequencies of Tregs within the peripheral circulation and tumor microenvironment of cancer patients correlate with poor prognosis and reduced survival. Understanding the mechanism of Treg elevation is critical for the development of new approaches aiming to modulate the frequency and function of Tregs to enhance the efficacy of cancer immune-based therapies.
This review focuses on current knowledge concerning Tregs in cancer and discusses putative mechanisms which underlie the expansion of Tregs in cancer patients. Additionally, we review current strategies to deplete/suppress Treg activity, the limitations of these strategies and future perspective for improving their efficacy.
An insight of the current aspects concerning Treg subsets in cancer and an overview of recent advances in the identification of Treg-specific markers, in addition to the potential strategies to target Tregs for enhancing antitumor immunity.
Mechanisms by which Treg functions modulate the immune response to tumors are becoming further understood. However, specific markers to tumor-specific/induced Tregs are yet to be clearly identified, which is a major limitation in optimizing strategies to specifically target Tregs in cancer. Despite this, strategies aimed at modulating Tregs in patients are providing some early encouraging results supporting the overall concept and indicating that further studies are clearly warranted.
主动抑制针对肿瘤的免疫反应是癌症免疫疗法成功的主要障碍。现在有确凿的证据表明调节性 T 细胞(Tregs)是驱动免疫抑制的关键因素。癌症患者外周循环和肿瘤微环境中 Tregs 的频率升高与预后不良和生存率降低相关。了解 Treg 升高的机制对于开发旨在调节 Treg 的频率和功能以增强癌症免疫治疗效果的新方法至关重要。
本篇综述的重点是关于癌症中 Tregs 的现有知识,并讨论了导致癌症患者 Tregs 扩增的潜在机制。此外,我们还回顾了目前耗竭/抑制 Treg 活性的策略、这些策略的局限性以及提高其疗效的未来展望。
对癌症中 Treg 亚群的当前方面的深入了解,以及对 Treg 特异性标志物的最新进展的概述,此外还有针对 Tregs 以增强抗肿瘤免疫的潜在策略。
Treg 功能调节肿瘤免疫反应的机制正在进一步理解。然而,尚未明确鉴定出针对肿瘤特异性/诱导性 Tregs 的特异性标志物,这是优化针对癌症中 Tregs 的特定靶向策略的主要限制。尽管如此,旨在调节患者 Tregs 的策略正在提供一些早期令人鼓舞的结果,支持总体概念,并表明进一步的研究显然是必要的。