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Immune Checkpoint Blockade in Cancer Immunotherapy: Mechanisms, Clinical Outcomes, and Safety Profiles of PD-1/PD-L1 Inhibitors
Archivum Immunologiae et Therapiae Experimentalis ( IF 2.9 ) Pub Date : 2020-11-13 , DOI: 10.1007/s00005-020-00601-6
Yan Yan 1 , Li Zhang 2, 3 , Yun Zuo 1 , Heya Qian 1 , Chang Liu 4
Affiliation  

Programmed cell death protein 1 (PD-1) and its ligand PD-L1 are critical for the regulation of T cell exhaustion and activity suppression. Tumor cells expressing immune checkpoints including PD-L1 escape monitoring of T cells from the host immune system. Checkpoint inhibitors are highly promising therapies that function as tumor-suppressing factors via modulation of tumor cell–immune cell interactions as well as boosting T cell-mediated anti-tumor immunity. Notably, PD-1 or PD-L1 monoclonal antibody (mAb) has demonstrated promising therapeutic effects in clinical studies of many types of cancer. These mAbs have caused significant tumor regression with impressive anti-tumor response rates as well as a favorable safety profile in cancer patients. Furthermore, the combination of PD-1/PD-L1 mAbs with other types of anti-tumor agents has also developed to boost the anti-tumor responses and enhance therapeutic effects in cancer patients. This review clarifies the mechanisms of PD-1/PD-L1-mediated anti-cancer immune responses and some clinical studies of mAbs targeting PD-1/PD-L1. The challenges and future of PD-1/PD-L1 blockade therapy are also discussed.



中文翻译:

癌症免疫治疗中的免疫检查点封锁:PD-1 / PD-L1抑制剂的机制,临床结果和安全性

程序性细胞死亡蛋白1(PD-1)及其配体PD-L1对于调节T细胞衰竭和抑制活性至关重要。表达免疫检查点(包括PD-L1)的肿瘤细胞逃脱了宿主免疫系统对T细胞的监测,检查点抑制剂是极有前途的疗法,可通过调节肿瘤细胞与免疫细胞的相互作用以及增强T细胞介导的作用而充当肿瘤抑制因子抗肿瘤免疫力。值得注意的是,PD-1或PD-L1单克隆抗体(mAb)在许多类型的癌症的临床研究中均显示出令人鼓舞的治疗效果。这些单克隆抗体在癌症患者中引起了显着的肿瘤消退,并具有令人印象深刻的抗肿瘤反应率以及良好的安全性。此外,PD-1 / PD-L1 mAb与其他类型的抗肿瘤药物的组合也得到了发展,以增强抗肿瘤反应并增强癌症患者的治疗效果。这篇综述阐明了PD-1 / PD-L1介导的抗癌免疫反应的机制,以及针对PD-1 / PD-L1的mAb的一些临床研究。还讨论了PD-1 / PD-L1阻断疗法的挑战和未来。

更新日期:2020-11-13
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