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免疫检查点与癌症信号通路的联合治疗为卵巢癌治疗提供了新视角。

Combinatorial therapy of immune checkpoint and cancer pathways provides a novel perspective on ovarian cancer treatment.

作者信息

Zhang Guyu, Liu Chongdong, Bai Huiming, Cao Guangming, Cui Ran, Zhang Zhengyu

机构信息

Department of Gynecology and Obstetrics, Beijing Chaoyang Hospital, Capital Medical University, Beijing 10000, P.R. China.

出版信息

Oncol Lett. 2019 Mar;17(3):2583-2591. doi: 10.3892/ol.2019.9902. Epub 2019 Jan 8.

Abstract

An increasing number of studies have reported that immunotherapy serves a significant role in ovarian cancer treatment. In recent years, blockade of checkpoint pathways, including programmed death-ligand 1 (PD-L1)/programmed death-1 and cytotoxic T-lymphocyte-associated protein 4, has demonstrated significant clinical and preclinical benefits in the treatment of ovarian cancer. Additionally, tumor-associated angiogenesis and homologous recombination deficiency frequently occurs in patients with high-grade ovarian cancer, which makes cancer cells more susceptible to targeted therapies, including therapies targeting poly (ADP-ribose) polymerase inhibitor, and anti-angiogenic approaches. Additionally, targeted therapy has been associated with elevated PD-L1 expression in tumor cells, increased T-cell infiltration in tumors and dendritic cell stimulation. This synergistic effect provides the rationale for the joint application of targeted therapy and immunotherapy. Checkpoint blockades are able to elicit durable antitumor immune reactions and complement the transient antitumor effect of targeted therapies. The current review discusses the underlying mechanism of these therapies and novel developments in combined therapy for the treatment of ovarian cancer.

摘要

越来越多的研究报告称免疫疗法在卵巢癌治疗中发挥着重要作用。近年来,对包括程序性死亡配体1(PD-L1)/程序性死亡1和细胞毒性T淋巴细胞相关蛋白4在内的检查点通路的阻断,已在卵巢癌治疗中显示出显著的临床和临床前益处。此外,肿瘤相关血管生成和同源重组缺陷在高级别卵巢癌患者中经常出现,这使得癌细胞更容易受到靶向治疗,包括靶向聚(ADP-核糖)聚合酶抑制剂的治疗和抗血管生成方法。此外,靶向治疗与肿瘤细胞中PD-L1表达升高、肿瘤中T细胞浸润增加以及树突状细胞刺激有关。这种协同效应为靶向治疗和免疫疗法的联合应用提供了理论依据。检查点阻断能够引发持久的抗肿瘤免疫反应,并补充靶向治疗的短暂抗肿瘤作用。本综述讨论了这些疗法的潜在机制以及卵巢癌联合治疗的新进展。

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