Honeychurch Jamie, Illidge Timothy M
Targeted Therapy Group, Division of Cancer Sciences, Manchester Cancer Research Centre, Christie Hospital, Manchester Academic Health Sciences Centre, National Institute of Health Research Biomedical Research Centre, Manchester, M20 4BX, UK.
Targeted Therapy Group, Division of Cancer Sciences, Manchester Cancer Research Centre, Christie Hospital, Manchester Academic Health Sciences Centre, National Institute of Health Research Biomedical Research Centre, Manchester, UK.
Ther Adv Vaccines Immunother. 2017 Dec;5(6):115-122. doi: 10.1177/2051013617750561. Epub 2018 Jan 24.
In addition to tumouricidal activity, radiotherapy is now recognized to display potent immunostimulatory properties that can contribute to the generation of anti-cancer immune responses. Treatment with radiation can induce a variety of pro-immunogenic and phenotypic changes in malignant cells, and recalibrate the immune contexture of the tumour microenvironment, leading to enhanced activation of the innate immune system, and priming of tumour-specific T-cell immunity. The immune-dependent effects of radiotherapy provide a sound rationale for the development of combination strategies, whereby the immunomodulatory properties of radiation can be exploited to augment the activity of immunotherapeutic agents. Encouraged by the recent success of breakthrough therapies such as immune checkpoint blockade, and a wealth of experimental data demonstrating the efficacy of radiotherapy and immunotherapy combinations, the clinical potential of this approach is now being explored in numerous trials. Successful translation will require careful consideration of the most suitable dose and fractionation of radiation, choice of immunotherapy and optimal sequencing and scheduling regimen. Immunological control of cancer is now becoming a clinical reality. There is considerable optimism that the development of effective radiotherapy and immunotherapy combinations with the capacity to induce durable, systemic immunity will further enhance patient outcome and transform the future management of cancer.
除了具有杀肿瘤活性外，现在人们认识到放疗还具有强大的免疫刺激特性，可有助于产生抗癌免疫反应。放疗可诱导恶性细胞发生多种促免疫原性和表型变化，并重新调整肿瘤微环境的免疫格局，从而增强先天免疫系统的激活，并启动肿瘤特异性T细胞免疫。放疗的免疫依赖性效应为联合治疗策略的发展提供了合理依据，据此可利用放疗的免疫调节特性来增强免疫治疗药物的活性。受免疫检查点阻断等突破性疗法近期成功的鼓舞，以及大量证明放疗与免疫治疗联合疗效的实验数据的推动，目前正在众多试验中探索这种方法的临床潜力。成功转化需要仔细考虑最合适的放疗剂量和分割方式、免疫治疗的选择以及最佳的序贯和给药方案。癌症的免疫控制现在正成为临床现实。人们相当乐观地认为，开发能够诱导持久全身免疫的有效放疗与免疫治疗联合方案将进一步改善患者预后，并改变癌症的未来治疗方式。
