Ionizing radiation has historically been used to treat cancer by killing tumour cells, in particular by inducing DNA damage. This view of radiotherapy (RT) as a simple cytotoxic agent has dramatically changed in recent years, and it is now widely accepted that RT can deeply reshape the tumour environment by modulating the immune response. Such evidence gives a strong rationale for the use of immunomodulators to boost the therapeutic value of RT, introducing the era of 'immunoradiotherapy'. The increasing amount of preclinical and clinical data concerning the combination of RT with immunomodulators, in particular with immune checkpoint inhibitors such as anti-PD-1/PD-L1 and anti-CTLA4, reflects the interest of the scientific and medical community concerning immunoradiotherapy. The expectations are enormous since the rationale for performing such combinations is strong, with the possibility to use a local treatment such as RT to amplify a systemic antitumour response, as illustrated by the case of the abscopal effect. Nevertheless, several points remain to be addressed such as the need to find biomarkers to identify patients who will benefit from immunoradiotherapy, the identification of the best sequences/schedules for combination with immunomodulators and mechanisms to overcome resistance. Additionally, the effects of immunoradiotherapy on healthy tissues and related toxicity remain largely unexplored. To answer these critical questions and make immunoradiotherapy keep its promising qualities, large efforts are needed from both the pharmaceutical industry and academic/governmental research. Moreover, because of the work of both these entities, the arsenal of available immunomodulators is quickly expanding, thus opening the field to increasing combinations with RT. We thus forecast that the field of immunoradiotherapy will further expand in the coming years, and it needs to be supported by appropriate investment plans.

中文翻译：

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放射疗法-免疫疗法组合——前景和挑战。

电离辐射历来被用于通过杀死肿瘤细胞来治疗癌症，特别是通过诱导 DNA 损伤。近年来，这种将放疗 (RT) 视为简单细胞毒剂的观点发生了巨大变化，现在人们普遍认为放疗可以通过调节免疫反应来深度重塑肿瘤环境。这些证据为使用免疫调节剂提高放疗的治疗价值提供了强有力的理由，从而开创了“免疫放射治疗”时代。越来越多的关于放疗与免疫调节剂联合使用的临床前和临床数据，特别是与免疫检查点抑制剂，如抗 PD-1/PD-L1 和抗 CTLA4 的结合，反映了科学和医学界对免疫放射治疗的兴趣。期望是巨大的，因为进行这种组合的理由很充分，并且有可能使用局部治疗（如放疗）来放大全身抗肿瘤反应，如远隔效应的情况所示。尽管如此，仍有几个问题需要解决，例如需要找到生物标志物来识别将从免疫放射治疗中受益的患者，识别与免疫调节剂组合的最佳序列/时间表以及克服耐药性的机制。此外，免疫放射疗法对健康组织的影响和相关毒性在很大程度上仍未得到探索。为了回答这些关键问题并使免疫放射疗法保持其有前途的品质，制药行业和学术/政府研究都需要付出巨大的努力。而且，由于这两个实体的工作，可用的免疫调节剂库正在迅速扩大，从而为增加与 RT 的组合开辟了领域。因此，我们预测未来几年免疫放射治疗领域将进一步扩大，需要适当的投资计划支持。