过去几年逐渐出现了越来越多的证据，表明放射治疗在免疫调节方面发挥着重要的作用。放射治疗重塑了肿瘤微环境，可以转变微环境的平衡到更具免疫刺激作用或免疫抑制作用。放射治疗的免疫反应似乎取决于照射配置（剂量、粒子种类、分次）和送达方式（剂量率、空间分布）。尽管最佳照射配置（剂量、时间分次、空间剂量分布等）尚未确定，但采用高剂量的时间方案似乎可以通过免疫原性细胞死亡促进辐照诱导的免疫反应。通过产生损伤相关的分子模式和感应双链DNA和RNA断裂，免疫原性细胞死亡激活先天性和适应性免疫反应，导致效应T细胞浸润肿瘤和周围疗效。新型放射治疗方法，如FLASH和空间分数剂量放射治疗（SFRT），强烈改变了剂量递送方法。FLASH-RT和SFRT具有有效激活免疫系统并保护周围健康组织的潜力。本文综述了这两种新放射治疗技术在肿瘤、健康免疫细胞和非靶向区域中的免疫调节效果及其与免疫治疗相结合的治疗潜力的现状。版权所有©2023 Elsevier Inc.保留所有权利。

The last several years have revealed increasing evidence of the immunomodulatory role of radiation therapy. Radiotherapy reshapes the tumoral microenvironment can shift the balance toward a more immunostimulatory or immunosuppressive microenvironment. The immune response to radiation therapy appears to depend on the irradiation configuration (dose, particle, fractionation) and delivery modes (dose rate, spatial distributions). Although an optimal irradiation configuration (dose, temporal fractionation, spatial dose distribution, etc.) has not yet been determined, temporal schemes employing high doses per fraction appear to favor radiation-induced immune response through immunogenic cell death. Through the release of damage-associated molecular patterns and the sensing of double-stranded DNA and RNA breaks, immunogenic cell death activates the innate and adaptive immune response, leading to tumor infiltration by effector T cells and the abscopal effect. Novel radiotherapy approaches such as FLASH and spatially fractionated radiotherapies (SFRT) strongly modulate the dose delivery method. FLASH-RT and SFRT have the potential to trigger the immune system effectively while preserving healthy surrounding tissues. This manuscript reviews the current state of knowledge on the immunomodulation effects of these two new radiotherapy techniques in the tumor, healthy immune cells and non-targeted regions, as well as their therapeutic potential in combination with immunotherapy.Copyright © 2023 Elsevier Inc. All rights reserved.