Zheng Dan, Hou Xiaolin, Yu Jing, He Xiujing
Laboratory of Integrative Medicine, Clinical Research Center for Breast, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, Chengdu, China.
Department of Neurosurgery, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China.
Front Pharmacol. 2022 Jul 22;13:928369. doi: 10.3389/fphar.2022.928369. eCollection 2022.
As an emerging antitumor strategy, immune checkpoint therapy is one of the most promising anticancer therapies due to its long response duration. Antibodies against the programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1) axis have been extensively applied to various cancers and have demonstrated unprecedented efficacy. Nevertheless, a poor response to monotherapy with anti-PD-1/PD-L1 has been observed in metastatic breast cancer. Combination therapy with other standard treatments is expected to overcome this limitation of PD-1/PD-L1 blockade in the treatment of breast cancer. In the present review, we first illustrate the biological functions of PD-1/PD-L1 and their role in maintaining immune homeostasis as well as protecting against immune-mediated tissue damage in a variety of microenvironments. Several combination therapy strategies for the combination of PD-1/PD-L1 blockade with standard treatment modalities have been proposed to solve the limitations of anti-PD-1/PD-L1 treatment, including chemotherapy, radiotherapy, targeted therapy, antiangiogenic therapy, and other immunotherapies. The corresponding clinical trials provide valuable estimates of treatment effects. Notably, several combination options significantly improve the response and efficacy of PD-1/PD-L1 blockade. This review provides a PD-1/PD-L1 clinical trial landscape survey in breast cancer to guide the development of more effective and less toxic combination therapies.
作为一种新兴的抗肿瘤策略，免疫检查点疗法因其较长的反应持续时间而成为最有前景的抗癌疗法之一。针对程序性死亡蛋白1（PD-1）和程序性死亡配体1（PD-L1）轴的抗体已广泛应用于各种癌症，并显示出前所未有的疗效。然而，在转移性乳腺癌中已观察到对抗PD-1/PD-L1单药治疗的反应不佳。与其他标准治疗联合有望克服PD-1/PD-L1阻断在乳腺癌治疗中的这一局限性。在本综述中，我们首先阐述PD-1/PD-L1的生物学功能及其在维持免疫稳态以及在多种微环境中防止免疫介导的组织损伤方面的作用。为解决抗PD-1/PD-L1治疗的局限性，已提出几种将PD-1/PD-L1阻断与标准治疗方式联合的联合治疗策略，包括化疗、放疗、靶向治疗、抗血管生成治疗和其他免疫疗法。相应的临床试验提供了对治疗效果的有价值评估。值得注意的是，几种联合方案显著提高了PD-1/PD-L1阻断的反应和疗效。本综述提供了乳腺癌中PD-1/PD-L1临床试验概况调查，以指导开发更有效且毒性更小的联合疗法。
