肿瘤免疫治疗中PD-1/PD-L1抑制剂的研究进展

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摘要程序性死亡因子-1（PD-1）及其配体PD-L1抑制剂通过阻断PD-1与PD-L1的结合而使负向调控信号受阻，导致T细胞恢复活性，从而增强免疫应答。目前已被批准上市的靶向PD-1/PD-L1药物主要有Nivolumab、Pembrolizumab、Atezolizumab等，临床研究结果显示PD-1/PD-L1抑制剂单药或联合ipilimumab治疗黑色素瘤、二线治疗PD-L1阳性的晚期非小细胞肺癌均有明确的效果，同时，应用于治疗乳腺癌、头颈癌、胃癌、尿路上皮癌、淋巴瘤等恶性肿瘤的临床试验正积极展开。目前PD-1/PD-L1抑制剂存在潜在的严重不良反应、治疗模式难以确定、疗效难以评价和价格昂贵等问题。本研究主要对PD-1/PD-L1抑制剂的作用机制、现况及其在不同肿瘤治疗中的应用效果进行综述，指出存在的问题，为后续研究和政府相关政策制定提供部分思路和依据。

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	刘永军▲ 徐稳

关键词 ：肿瘤, 免疫疗法, 程序性死亡因子-1, 程序性死亡因子-1配体

Abstract：Programmed cell death-1(PD-1) and its ligand PD-L1 inhibitors can inhibit PD-1 and PD-L1 combination to block negative control signals, leading to activity of T cells and enhancement of immune responses. Targeted PD-1/PD-L1 drugs currently approved for marketing include Nivolumab, Pembrolizumab, Atezolizumab, etc. Clinical studies have shown that PD-1/PD-L1 inhibitors have a definite effect on monotherapy or combined with ipilimumab for the treatment of melanoma and second-line treatment PD-L1 positive advanced non-small cell lung cancer. At the same time, clinical trials for the treatment of breast cancer, head and neck cancer, gastric cancer, urothelial cancer, lymphoma and other malignancies are actively underway. At present, PD-1/PD-L1 inhibitors have some problems such as potential serious adverse reactions, uncertain treatment model, difficult to evaluate efficacy and expensive price. This article mainly reviews the action mechanism and current situation of PD-1 and PD-L1 inhibitors as well as their application in the treatment of various tumors, points out the problems existing in the current research, and provides some ideas and basis for follow-up research and government related policy formulation.

Key words： Tumor Immunotherapy Programmed cell death-1 Programmed cell death-L1

基金资助:中国药科大学国际医药商学院资助项目（校合2015-商19）。

通讯作者: ▲通讯作者

作者简介: 刘永军（1973.5-），男，博士，副教授；研究方向：药物经济学和医师多点执业。

引用本文:

刘永军▲ 徐稳. 肿瘤免疫治疗中PD-1/PD-L1抑制剂的研究进展[J]. 中国医药导报, 2018, 15(16): 38-41.
LIU Yongjun▲ XU Wen. Advances of PD-1/PD-L1 inhibitors in tumor immunotherapy. 中国医药导报, 2018, 15(16): 38-41.

链接本文:

http://www.yiyaodaobao.com.cn/CN/ 或 http://www.yiyaodaobao.com.cn/CN/Y2018/V15/I16/38

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