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[免疫疗法与放射疗法]

[Immunotherapy and radiotherapy].

作者信息

Bockel S, Antoni D, Deutsch É, Mornex F

机构信息

Département universitaire de radiothérapie, centre Paul-Strauss, 3, rue de la Porte-de-l'Hôpital, 67065 Strasbourg cedex, France.

Département universitaire de radiothérapie, centre Paul-Strauss, 3, rue de la Porte-de-l'Hôpital, 67065 Strasbourg cedex, France; EA 3430, Fédération de médecine translationnelle de Strasbourg (FMTS), université de Strasbourg, 67000 Strasbourg cedex, France.

出版信息

Cancer Radiother. 2017 May;21(3):244-255. doi: 10.1016/j.canrad.2016.12.005. Epub 2017 May 15.

Abstract

Radiotherapy, primarily known for its cytotoxic effect on the tumor cells, via the induction of DNA damages, has the ability to induce a systemic antitumoral response. By an immunologic cell death, tumor cells exposed to radiation release a large amount of neoantigenes and pro-inflammatory mediators, acting as an in situ vaccine, resulting in an tumor regression within the primary irradiated site, but also in the distant "out of field" secondary tumors. However, this phenomenon is extremly rare with radiotherapy alone, suggesting that the radiation-induced antitumor immunity is not sufficient for overcoming the tumor's and its microenvironnement immunosuppressing effect. Over the last years, many scientific data and preclinical studies have demonstrated that the combination of local irradiation with immune therapy has a synergistic action in inducing an antitumoral immunity, thus enhancing an abscopal effect. In this article, we summarize the main mechanisms cancer harnesses to evade the control of the immune system and how ionising radiations can induce an antitumor immunity. A focus reports then on recent preclinical and clinical research built on this background of combined radiation and immune therapy, which bear the great potential to further improve anticancer therapies.

摘要

放射疗法主要因其通过诱导DNA损伤对肿瘤细胞产生细胞毒性作用而闻名,它有能力诱导全身性抗肿瘤反应。通过免疫性细胞死亡,暴露于辐射的肿瘤细胞会释放大量新抗原和促炎介质,起到原位疫苗的作用,导致原发性照射部位的肿瘤消退,同时也能使远处“野外”的继发性肿瘤消退。然而,这种现象在单独使用放射疗法时极为罕见,这表明辐射诱导的抗肿瘤免疫不足以克服肿瘤及其微环境的免疫抑制作用。在过去几年中,许多科学数据和临床前研究表明,局部照射与免疫疗法相结合在诱导抗肿瘤免疫方面具有协同作用,从而增强远隔效应。在本文中,我们总结了癌症用于逃避免疫系统控制的主要机制,以及电离辐射如何诱导抗肿瘤免疫。随后重点报道了基于这种放射与免疫联合治疗背景的近期临床前和临床研究,这些研究具有进一步改善抗癌治疗的巨大潜力。

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