Role of T lymphocytes in tumor response to radiotherapy.
Role of T lymphocytes in tumor response to radiotherapy.
复制标题
DOI：
10.3389/fonc.2012.00095
复制
发表时间：
2012
影响因子：
4.7
通讯作者：
Formenti SC
中科院分区：
文献类型：
--
作者：
Demaria S;Formenti SC
三十多年前，海伦·斯通和他的同事比较了免疫活性和T细胞缺陷小鼠局部肿瘤照射的效果，提供了第一个证据，表明在缺乏正常T细胞库的情况下，肿瘤对放射治疗的反应受到损害。在接下来的三十年里，人们对T细胞及其调节其激活、向肿瘤迁移和效应器功能的复杂分子机制的了解呈指数级增长。我们现在还知道，肿瘤进展与多种免疫抑制机制的发展有内在联系，这些机制允许癌细胞逃避免疫控制。最近关于T细胞在决定癌症任何临床阶段患者的预后和结局中的作用的证据，有助于将免疫监测和免疫编辑的概念从临床前模型领域重新引导到临床观察的现实中。重要的是，化疗和放射等标准抗癌疗法导致的细胞死亡已被证明涉及免疫系统，并在某些特定环境中启用特定的免疫反应。因此，在过去的几年里，探索如何利用辐射诱导抗肿瘤免疫反应的研究有所增加，这并不令人惊讶。我们将对抗肿瘤T细胞在放射治疗肿瘤控制中起关键作用的实验证据进行综述。辐射对肿瘤的影响已被证明增强了抗肿瘤免疫的启动和效应阶段，将被讨论。最后，我们将重点介绍免疫反应调节剂与放射治疗的前景光明的组合，这些药物可以增强T细胞功能，目前正在进行临床测试。
Over thirty years ago, Helen Stone and colleagues compared the effects of local tumor irradiation in immunocompetent and T cell deficient mice, providing the first evidence that tumor response to radiotherapy is impaired in the absence of a normal T cell repertoire. In the following three decades there has been an exponential growth in understanding T cells and the complex molecular mechanisms that regulate their activation, migration to tumors and effector functions. We now also know that tumor progression is intrinsically linked to the development of multiple immunosuppressive mechanisms that allow cancer cells to escape immune control. Recent evidence about the role of T cells in determining the prognosis and outcome of patients at any clinical stages of cancer has been instrumental in re-directing the concept of immunosurveillance and immunoediting from the realm of preclinical models to the reality of clinical observations. Importantly, cell death induced by standard anti-cancer therapies like chemotherapy and radiation has been demonstrated to involve the immune system and, in certain specific settings, enable a specific immune response. It is, therefore, not surprising that the last few years have seen an increase in investigations exploring how to harness the ability of radiation to induce anti-tumor immune responses. We will review here the experimental evidence that anti-tumor T cells are key players in tumor control achieved by radiotherapy. The effects of radiation on the tumor that have been shown to enhance the priming and effector phases of anti-tumor immunity will be discussed. Finally, we will highlight promising combinations of immune response modifiers that enhance T cell function with radiotherapy which are being tested in the clinic.