Radiation as an immunological adjuvant: current evidence on dose and fractionation.
Radiation as an immunological adjuvant: current evidence on dose and fractionation.
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DOI：
10.3389/fonc.2012.00153
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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
对癌症部位的电离辐射具有将被照射的肿瘤转化为免疫原性枢纽的能力。然而，辐射是肿瘤微环境的复杂改性剂，并且其本身很少足以诱导治疗上显著的抗肿瘤免疫应答，因为它还可以激活免疫抑制途径。虽然在临床前模型中已经显示局部放射和免疫疗法的几种组合诱导强大的抗肿瘤免疫，但实现这种效果的最佳策略仍有待确定。当在体内使用时，对肿瘤的辐射效应取决于所施加的每部分的剂量、所使用的部分的数量和总剂量。此外，这三个变量的相互作用取决于所研究的肿瘤环境，无论是在临床前还是临床应用中。为了能够修复对正常组织的附带损伤，通常以多个部分给予辐射，通常为2戈伊。通常，较大部分的使用限于立体定向应用，由此最佳固定减少了部分间和部分内移动，并允许将剂量非常适形地递送到靶，同时最佳地排除正常组织。将放射和免疫疗法的伙伴关系转化为临床需要仔细考虑所使用的放射方案。迄今为止，关于不同剂量/分次方案是否对抗肿瘤免疫应答具有特定影响知之甚少。大多数结合两种模式的实验都是用单次放疗进行的。然而，至少有一些证据表明，当与一些特定的免疫治疗方法相结合时，辐射促进抗肿瘤免疫的能力取决于所采用的剂量和分割。我们批判性地回顾了关于这一主题的体外和体内数据，并讨论了分割对放射与免疫疗法协同作用能力的潜在影响。
Ionizing radiation to a cancer site has the ability to convert the irradiated tumor in an immunogenic hub. However, radiation is a complex modifier of the tumor microenvironment and, by itself, is seldom sufficient to induce a therapeutically significant anti-tumor immune response, since it can also activate immune suppressive pathways. While several combinations of local radiation and immunotherapy have been shown in pre-clinical models to induce powerful anti-tumor immunity, the optimal strategy to achieve this effect remains to be defined. When used in vivo, radiation effects on tumors depend on the dose per fraction applied, the number of fractions used, and the total dose. Moreover, the interplay of these three variables is contingent upon the tumor setting studied, both in pre-clinical and clinical applications. To enable repair of the collateral damage to the normal tissue, radiation is usually given in multiple fractions, usually of 2 Gy. Generally, the use of larger fractions is limited to stereotactic applications, whereby optimal immobilization reduces inter- and intrafraction movement and permits a very conformal delivery of dose to the target, with optimal exclusion of normal tissue. Translation of the partnership of radiation and immunotherapy to the clinic requires a careful consideration of the radiation regimens used. To date, little is known on whether different dose/fractionation regimens have a specific impact on the anti-tumor immune response. Most experiments combining the two modalities were conducted with single fractions of radiotherapy. However, there is at least some evidencethat when combined with some specific immunotherapy approaches, the ability of radiation to promote anti-tumor immunity is dependent on the dose and fractionation employed. We critically review the available in vitro and in vivo data on this subject and discuss the potential impact of fractionation on the ability of radiation to synergize with immunotherapy.