Department of Radiation Oncology and Biomedical Sciences, Cedars-Sinai Medical, 8700 Beverly Blvd, Los Angeles, USA.
Philips Institute for Oral Health Research, School of Dentistry Virginia Commonwealth University, Richmond, VA, 23298, USA.
Clin Transl Oncol. 2022 Dec;24(12):2255-2271. doi: 10.1007/s12094-022-02888-7. Epub 2022 Aug 1.
Radiotherapy (RT), unlike chemotherapy, is one of the most routinely used and effective genotoxic and immune response inducing cancer therapies with an advantage of reduced side effects. However, cancer can relapse after RT owing to multiple factors, including acquired tumor resistance, immune suppressive microenvironment buildup, increased DNA repair, thus favoring tumor metastasis. Efforts to mitigate these undesirable effects have drawn interest in combining RT with immunotherapy, particularly the use of immune checkpoint inhibitors, to tilt the pre-existing tumor stromal microenvironment into long-lasting therapy-induced antitumor immunity at multiple metastatic sites (abscopal effects). This multimodal therapeutic strategy can alleviate the increased T cell priming and decrease tumor growth and metastasis, thus emerging as a significant approach to sustain as long-term antitumor immunity. To understand more about this synergism, a detailed cellular mechanism underlying the dynamic interaction between tumor and immune cells within the irradiated tumor microenvironment needs to be explored. Hence, in the present review, we have attempted to evaluate various RT-inducible immune factors, which can be targeted by immunotherapy and provide detailed explanation to optimally maximize their synergy with immunotherapy for long-lasting antitumor immunity. Moreover, we have critically assessed various combinatorial approaches along with their challenges and described strategies to modify them in addition to providing approaches for optimal synergistic effects of the combination.
放疗（RT）与化疗不同，是最常规使用且有效的诱导肿瘤发生遗传毒性和免疫反应的癌症治疗方法之一，其副作用较小。然而，由于多种因素，包括获得性肿瘤耐药性、免疫抑制微环境的建立、增加的 DNA 修复，癌症在 RT 后可能会复发，从而有利于肿瘤转移。为了减轻这些不良影响，人们对将 RT 与免疫疗法结合产生了兴趣，特别是使用免疫检查点抑制剂，将预先存在的肿瘤基质微环境转变为多个转移部位的持久治疗诱导抗肿瘤免疫（远隔效应）。这种多模式治疗策略可以减轻 T 细胞的初始激活，减少肿瘤生长和转移，因此成为维持长期抗肿瘤免疫的重要方法。为了更深入地了解这种协同作用，需要探索辐照肿瘤微环境中肿瘤和免疫细胞之间动态相互作用的详细细胞机制。因此，在本综述中，我们试图评估各种可通过免疫疗法靶向的 RT 诱导免疫因子，并对其进行详细解释，以最大限度地提高其与免疫疗法的协同作用，从而产生持久的抗肿瘤免疫。此外，我们还批判性地评估了各种联合治疗方法及其挑战，并描述了对其进行修饰的策略，以及提供了优化联合治疗协同作用的方法。
