立体定向放疗联合免疫治疗晚期恶性肿瘤进展

Progress in stereotactic body radiation therapy combined with immunotherapy for advanced malignancies

晚期肺转移癌或黑素瘤中放疗联合免疫检测点抑制剂,封闭免疫抑制通路,增强抗肿瘤免疫应答,在临床上明显改善生存。体部立体定向放疗大剂量精准照射到肿瘤靶区,最大程度避免周围正常组织损伤,同时还诱导相关细胞因子和免疫分子表达,较常规放疗更能诱导强烈的免疫反应及远隔效应,更适合与免疫联合。已有研究表明总剂量和分割模式是调节放疗免疫反应的重要参数;放疗与免疫序贯时机显著影响疗效,肿瘤浸润淋巴细胞、PD-L1表达水平和MMR缺陷可能是预测放疗免疫治疗的重要指标。采用合理的放疗剂量和分割模式,选择最佳序贯时机和有效的预测标记物,SBRT联合免疫可以最大程度激活全身免疫反应,发挥远隔效应协同作用晚期恶性肿瘤。

For advanced pulmonary metastases or melanoma, radiotherapy combined with immune checkpoint inhibitor can block the immunosuppression pathway, enhance the antitumor immune response, and significantly improve survival. Stereotactic body radiation therapy （SBRT） delivers a large dose of radiation to the tumor target with high precision while sparing irradiation of the surrounding normal tissues. It is suggested that SBRT could be the most appropriate radiotherapy modality to be combined with immunotherapy since it induces the expression of a series of cytokines and immune molecules and is more likely to cause intense immune response and exert an abscopal effect than conventional radiotherapy. Previous studies have explored that total dose and fractionation seem to be important parameters for determining the immune response;the timing of radiation with immunotherapy significantly influences the outcome, and tumor infiltrating lymphocytes, the expression level of programmed death-ligand 1, and mismatch repair defect may be important predicators of the outcome. With appropriate radiotherapy dose and fractionation, the optimal timing of radiation with immunotherapy, and effective predictive markers, a combination of SBRT and immunotherapy may eliminate advanced malignancies while activating the systemic immune response to exert an abscopal effect.