Several immune checkpoint blockades (ICBs) capable of overcoming the immunosuppressive roles of the tumor immune microenvironment have been approved by the US Food and Drug Administration as front-line treatments of various tumor types. However, due to the considerable heterogeneity of solid tumor cells, inhibiting one target will only influence a portion of the tumor cells. One way to enhance the tumor-killing efficiency is to develop a multiagent therapeutic strategy targeting different aspects of tumor biology and the microenvironment to provide the maximal clinical benefit for patients with late-stage disease. One such strategy is the administration of anti-PD1, an ICB, in combination with the humanized monoclonal antibody bevacizumab, an anti-angiogenic therapy, to patients with recurrent/metastatic malignancies, including hepatocellular carcinoma, metastatic renal cell carcinoma, non-small cell lung cancer, and uterine cancer. Radiotherapy (RT), a critical component of solid cancer management, has the capacity to prime the immune system for an adaptive antitumor response. Here, we present an overview of the most recent published data in preclinical and clinical studies elucidating that RT could further potentiate the antitumor effects of immune checkpoint and angiogenesis dual blockade. In addition, we explore opportunities of triple combinational treatment, as well as discuss the challenges of validating biomarkers and the management of associated toxicity.

几种能够克服肿瘤免疫微环境的免疫抑制作用的免疫检查点封锁 (ICB) 已被美国食品和药物管理局批准作为各种肿瘤类型的一线治疗。然而，由于实体瘤细胞具有相当大的异质性，抑制一个靶点只会影响一部分肿瘤细胞。提高肿瘤杀伤效率的一种方法是开发针对肿瘤生物学和微环境不同方面的多药治疗策略，为晚期疾病患者提供最大的临床益处。一种这样的策略是将抗 PD1（一种 ICB）与人源化单克隆抗体贝伐珠单抗（一种抗血管生成疗法）联合用于复发/转移性恶性肿瘤患者，包括肝细胞癌、转移性肾细胞癌、非小细胞肺癌和子宫癌。放疗 (RT) 是实体癌管理的重要组成部分，能够启动免疫系统以产生适应性抗肿瘤反应。在这里，我们概述了临床前和临床研究中最近发表的数据，这些数据阐明了 RT 可以进一步增强免疫检查点和血管生成双重阻断的抗肿瘤作用。此外，我们探索了三重联合治疗的机会，并讨论了验证生物标志物和相关毒性管理的挑战。有能力启动免疫系统以产生适应性抗肿瘤反应。在这里，我们概述了临床前和临床研究中最近发表的数据，这些数据阐明了 RT 可以进一步增强免疫检查点和血管生成双重阻断的抗肿瘤作用。此外，我们探索了三重联合治疗的机会，并讨论了验证生物标志物和相关毒性管理的挑战。有能力启动免疫系统以产生适应性抗肿瘤反应。在这里，我们概述了临床前和临床研究中最近发表的数据，这些数据阐明了 RT 可以进一步增强免疫检查点和血管生成双重阻断的抗肿瘤作用。此外，我们探索了三重联合治疗的机会，并讨论了验证生物标志物和相关毒性管理的挑战。