抗肿瘤PD-1和PD-L1治疗现状与免疫相关不良反应的机制探索

doi:10.12114/j.issn.1007-9572.2021.01.312

摘要/Abstract

摘要： 程序性细胞死亡蛋白-1（PD-1）和程序性细胞死亡配体1（PD-L1）抑制剂是一组免疫检查点抑制剂，自2006年5月起，已经有10种靶向PD-1和PD-L1的免疫检查点抑制剂用于肿瘤治疗。尽管PD-1和PD-L1抑制剂对某些肿瘤显示出良好的治疗效果，但是严重的免疫相关不良反应限制了其临床应用。因此，研发同等疗效但不良反应较PD-1/PD-L1抑制剂少的新型药物迫在眉睫。此外，探索免疫相关不良反应的发生机制可以为制定个性化的干预策略提供依据，在PD-1和PD-L1抑制剂研究中的地位同样重要。本综述讨论了几种抗PD-1/PD-L1单克隆抗体的作用机制及免疫相关不良反应，旨在提醒临床医生在进行抗肿瘤治疗的同时需要监控相关不良反应的发生。此外，本综述还指出了未来PD-1/PD-L1抑制剂可能的研究方向。

关键词: 抗肿瘤药, 免疫, 程序性细胞死亡蛋白-1, 程序性细胞死亡配体1, 免疫抑制剂, 单克隆抗体, 不良反应

Abstract:

Programmed cell death protein-1 (PD-1) and programmed death ligand 1 (PD-L1) inhibitors are a group of immune checkpoint inhibitors. Since May 2006, there have been 10 immune checkpoint inhibitors targeting PD-1 and PD-L1 for tumor treatment. Although PD-1/PD-L1 inhibitors show promising curative effects on certain tumors, serious immune-related adverse events limited the clinical application. Therefore, it is urgent to develop new drugs with the same efficacy but fewer side effects than PD-1/PD-L1 inhibitors. In addition, exploring the mechanisms of immune-related adverse events provides a scientific foundation for developing personalized intervention strategies, which is equally important in the research of PD-1/PD-L1 inhibitors. This review discusses the mechanism and immune-related adverse events of several anti-PD-1/PD-L1 monoclonal antibodies, aiming at reminding clinicians of the occurrence of related adverse events while performing anti-tumor therapy. Moreover, this review also points out the possible research direction of PD-1/PD-L1 inhibitors in the future.

Key words: Antineoplastic agents, immunological, Programmed cell death protein 1, Programmed death ligand 1, Immunosuppressive agents, Monoclonal antibody, Adverse event

中图分类号:

R979.1 R979.5

杨蕾伊,林桑,谢其冰,等. 抗肿瘤PD-1和PD-L1治疗现状与免疫相关不良反应的机制探索[J]. 中国全科医学, 2022, 25(11): 1393-1398. DOI: 10.12114/j.issn.1007-9572.2021.01.312.

YANG Leiyi, LIN Sang, XIE Qibing, YIN Geng.

Current Status of PD-1/PD-L1 Anti-tumor Therapy and Exploration of the Mechanism of Immune-related Adverse Events [J]. Chinese General Practice, 2022, 25(11): 1393-1398.

图/表 1

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不良反应	Pembrolizumab^[53]	Nivolumab^[54]	Cemiplimab^[55]	Toripalimab^[36]	Sintilimab^[56]	Camrelizumab^[57]	Atezolizumab^[58]	Durvalumab^[59]
甲状腺功能减退	14.3%	0.3%	10.2%	12.1%	20%	22.2%	0.32%	-
甲状腺功能亢进	10.2%	0.1%	-	-	-	-	-	-
垂体炎	2.2%	0.4%	-	-	-	-	-	-
1型糖尿病	1.0%	0.1%	-	-	0	-	-	0.21%
肾上腺功能不全	1.0%	-	-	-	-	-	-	-
肺炎或间质性肺疾病	3.3%	1.0%	7.7%	8.6%	11%	2.2%	-	3.58%
严重皮肤反应	0.6%	0.3%	1.3%	0	0	0	0.32%	-
自身免疫性肝炎	1.8%	0.8%	1.3%	-	-	-	0.32%	-
结肠炎	3.7%	0.7%	1.3%	-	-	-	0.32%	-
胰腺炎	0.4%	-	-	-	-	-	-	-
肾炎	0.4%	0.9%	-	-	-	-	1.61%	0.42%
葡萄膜炎	0.4%	-	-	-	-	-	-	-
心肌炎	0.2%	0.1%	1.3%	-	1%	-	-	0.42%
血小板减少	-	-	-	8.6%	10%	17.7%	-	-

不良反应	Pembrolizumab^[53]	Nivolumab^[54]	Cemiplimab^[55]	Toripalimab^[36]	Sintilimab^[56]	Camrelizumab^[57]	Atezolizumab^[58]	Durvalumab^[59]
甲状腺功能减退	14.3%	0.3%	10.2%	12.1%	20%	22.2%	0.32%	-
甲状腺功能亢进	10.2%	0.1%	-	-	-	-	-	-
垂体炎	2.2%	0.4%	-	-	-	-	-	-
1型糖尿病	1.0%	0.1%	-	-	0	-	-	0.21%
肾上腺功能不全	1.0%	-	-	-	-	-	-	-
肺炎或间质性肺疾病	3.3%	1.0%	7.7%	8.6%	11%	2.2%	-	3.58%
严重皮肤反应	0.6%	0.3%	1.3%	0	0	0	0.32%	-
自身免疫性肝炎	1.8%	0.8%	1.3%	-	-	-	0.32%	-
结肠炎	3.7%	0.7%	1.3%	-	-	-	0.32%	-
胰腺炎	0.4%	-	-	-	-	-	-	-
肾炎	0.4%	0.9%	-	-	-	-	1.61%	0.42%
葡萄膜炎	0.4%	-	-	-	-	-	-	-
心肌炎	0.2%	0.1%	1.3%	-	1%	-	-	0.42%
血小板减少	-	-	-	8.6%	10%	17.7%	-	-