Department of Radiation Oncology, Capital Medical University Xuanwu Hospital, Beijing, China.
School of Basic Medical Sciences, Capital Medical University, Beijing, China.
Front Immunol. 2023 Jun 12;14:1125905. doi: 10.3389/fimmu.2023.1125905. eCollection 2023.
Immunotherapy consisted mainly of immune checkpoint inhibitors (ICIs) has led to significantly improved antitumor response. However, such response has been observed only in tumors possessing an overall responsive tumor immune micro-environment (TIME), in which the presence of functional tumor-infiltrating lymphocytes (TILs) is critical. Various mechanisms of immune escape from immunosurveillance exist, leading to different TIME phenotypes in correlation with primary or acquired resistance to ICIs. Radiotherapy has been shown to induce antitumor immunity not only in the irradiated primary tumor, but also at unirradiated distant sites of metastases. Such antitumor immunity is mainly elicited by radiation's stimulatory effects on antigenicity and adjuvanticity. Furthermore, it may be significantly augmented when irradiation is combined with immunotherapy, such as ICIs. Therefore, radiotherapy represents one potential therapeutic strategy to restore anti-tumor immunity in tumors presenting with an unresponsive TIME. In this review, the generation of anti-tumor immunity, its impairment, radiation's immunogenic properties, and the antitumor effects of combining radiation with immunotherapy will be comprehensively discussed.
免疫疗法主要包括免疫检查点抑制剂（ICIs），已导致抗肿瘤反应显著改善。然而，这种反应仅在具有整体反应性肿瘤免疫微环境（TIME）的肿瘤中观察到，其中功能性肿瘤浸润淋巴细胞（TILs）的存在是至关重要的。存在各种免疫逃避机制，导致与原发性或获得性对 ICI 的耐药性相关的不同 TIME 表型。放射治疗已被证明不仅在照射的原发肿瘤中，而且在未照射的转移远处部位也能诱导抗肿瘤免疫。这种抗肿瘤免疫主要是由放射对抗原性和佐剂性的刺激作用引起的。此外，当放疗与免疫疗法（如 ICI）联合使用时，其效果可能会显著增强。因此，放疗代表了一种潜在的治疗策略，可恢复呈现无反应性 TIME 的肿瘤中的抗肿瘤免疫。在这篇综述中，将全面讨论抗肿瘤免疫的产生、其受损、放射的免疫原性特性以及放疗与免疫疗法联合的抗肿瘤作用。
