Zhao Xinrui, Shao Chunlin
Institute of Radiation Medicine, Shanghai Medical College, Fudan University, No.2094 Xie-Tu Road, Shanghai 200032, China.
Cancers (Basel). 2020 Sep 25;12(10):2762. doi: 10.3390/cancers12102762.
Radiotherapy (RT) is a conventional method for clinical treatment of local tumors, which can induce tumor-specific immune response and cause the shrinkage of primary tumor and distal metastases via mediating tumor infiltration of CD8+ T cells. Ionizing radiation (IR) induced tumor regression outside the radiation field is termed as abscopal effect. However, due to the mobilization of immunosuppressive signals by IR, the activated CD8+T cells are not sufficient to maintain a long-term positive feedback to make the tumors regress completely. Eventually, the "hot" tumors gradually turn to "cold". With the advent of emerging immunotherapy, the combination of immune checkpoint blockade (ICB) and local RT has produced welcome changes in stubborn metastases, especially anti-PD-1/PD-L1 and anti-CTLA-4 which have been approved in clinical cancer treatment. However, the detailed mechanism of the abscopal effect induced by combined therapy is still unclear. Therefore, how to formulate a therapeutic schedule to maximize the efficacy should be took into consideration according to specific circumstance. This paper reviewed the recent research progresses in immunomodulatory effects of local radiotherapy on the tumor microenvironment, as well as the unique advantage for abscopal effect when combined with ICB, with a view to exploring the potential application value of radioimmunotherapy in clinic.
放射疗法（RT）是局部肿瘤临床治疗的传统方法，它可诱导肿瘤特异性免疫反应，并通过介导CD8 + T细胞浸润肿瘤，导致原发性肿瘤和远处转移灶缩小。电离辐射（IR）在辐射野外诱导的肿瘤消退被称为远隔效应。然而，由于IR会调动免疫抑制信号，活化的CD8 + T细胞不足以维持长期的正反馈，使肿瘤完全消退。最终，“热”肿瘤逐渐转变为“冷”肿瘤。随着新兴免疫疗法的出现，免疫检查点阻断（ICB）与局部RT的联合应用在顽固性转移瘤治疗中产生了可喜的变化，尤其是抗PD-1/PD-L1和抗CTLA-4已被批准用于临床癌症治疗。然而，联合治疗诱导远隔效应的具体机制仍不清楚。因此，应根据具体情况考虑如何制定治疗方案以最大化疗效。本文综述了局部放疗对肿瘤微环境免疫调节作用的最新研究进展，以及与ICB联合时远隔效应的独特优势，以期探索放射免疫疗法在临床上的潜在应用价值。
