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中华实验和临床感染病杂志(电子版)

中华实验和临床感染病杂志(电子版) ›› 2021, Vol. 15 ›› Issue (03) : 145 -148. doi: 10.3877/cma.j.issn.1674-1358.2021.03.001

综述

程序性死亡受体1/程序性死亡配体在结核分枝杆菌感染免疫中的作用和宿主导向治疗前景
张丽帆1, 杨峥蓉2, 刘晓清1,†()   
  1. 1. 100730　北京，中国医学科学院北京协和医学院，北京协和医院，疑难重症及罕见病国家重点实验室，感染内科；100730　北京，中国医学科学院北京协和医学院，国际临床流行病学网，临床流行病学教研室；100730　北京，中国医学科学院北京协和医学院，结核病研究中心
    2. 100730　北京，中国医学科学院北京协和医学院，北京协和医院，疑难重症及罕见病国家重点实验室，感染内科
  • 收稿日期:2020-06-24 出版日期:2021-06-15
  • 通信作者: 刘晓清
  • 基金资助:
    艾滋病和病毒性肝炎等传染病科技重大专项课题(No. 2017ZX10201302); 中国医学科学院医学与健康科技创新工程项目(No. 2016-I2M-1-013、2019-I2M-2-005); 中国医学科学院北京协和医学院中央级公益性科研院所基本科研业务项目(No. 2017PT31010)

Immune role of programmed death 1/programmed death-ligand pathway in Mycobacterium tuberculosis infection and prospects for host-directed therapy

Lifan Zhang1, Zhengrong Yang2, Xiaoqing Liu1,†()   

  1. 1. Division of Infectious Diseases, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China; Clinical Epidemiology Unit, International Epidemiology Network, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Beijing 100730, China; Centre for Tuberculosis Research, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
    2. Division of Infectious Diseases, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China
  • Received:2020-06-24 Published:2021-06-15
  • Corresponding author: Xiaoqing Liu
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张丽帆, 杨峥蓉, 刘晓清. 程序性死亡受体1/程序性死亡配体在结核分枝杆菌感染免疫中的作用和宿主导向治疗前景[J]. 中华实验和临床感染病杂志(电子版), 2021, 15(03): 145-148.

Lifan Zhang, Zhengrong Yang, Xiaoqing Liu. Immune role of programmed death 1/programmed death-ligand pathway in Mycobacterium tuberculosis infection and prospects for host-directed therapy[J]. Chinese Journal of Experimental and Clinical Infectious Diseases(Electronic Edition), 2021, 15(03): 145-148.

程序性死亡受体1（PD-1）/程序性死亡配体（PD-L）信号转导通路作为近年来的研究热点，其对恶性肿瘤的显著疗效为慢性感染性疾病患者的治疗提供了新思路。但应用PD-1抑制剂治疗恶性肿瘤过程中，出现结核分枝杆菌感染再活动的个案报道呈增加趋势。结核病是由结核分枝杆菌（MTB）感染所致，是由单一致病菌致病导致死亡病例最多的疾病，严重危害人们的健康。潜伏性结核分枝杆菌感染（LTBI）是MTB在体内的稽留状态，LTBI在特定条件下可发展为活动性结核病（ATB）。我国在结核病的防控工作方面始终面临着严峻挑战。本文就PD-1/PD-L信号转导通路在MTB感染免疫中的作用进行综述，为深入理解MTB宿主免疫以及探索新的结核病宿主导向治疗（HDT）方案提供线索。

关键词: 程序性死亡受体1/程序性死亡配体, 结核病, 潜伏性结核感染, T细胞免疫反应, 宿主导向治疗

The programmed death 1 (PD-1)/programmed death-ligand (PD-L) pathway had been a research hotspot in recent years, and its significant clinical benefit in patients with malignant tumors had provided new ideas for the treatment of patients with chronic infectious diseases. Cases of Mycobacteria tuberculosis (MTB) infection reactivity during PD-1 inhibitor treatment of malignant tumors have now been reported in the literature, which have shown a tendency to increase. Tuberculosis, a communicable disease caused by MTB, was a disease which cause the most number of deaths by a single pathogen. Latent MTB infection (LTBI) was pragmatically defined as infection with MTB. Latent tuberculosis infection could progress to active tuberculosis (ATB) under specific conditions. The epidemic situation of tuberculosis has brought severe challenges to the prevention and control of tuberculosis in China. This review discussed the immune role of PD-1/PD-L pathway in MTB infection and provides clues for in-depth understanding of MTB host immunity and exploring new tuberculosis host-directed therapy.

Key words: Programmed death 1/programmed death-ligand, Tuberculosis, Latent tuberculosis infection, T cell-mediated immunity, Host-directed therapy
表1 应用PD-1抑制剂的肿瘤患者发生活动性结核病的临床特点
参考文献 发表年份 性别 年龄 种族 肿瘤 药物 药物类型 确诊结核时间 诊断 结核部位 抗结核治疗方案 抗结核治疗结局
Byeon S等[4] 2020 女 57 亚洲 转移性非小细胞肺癌 纳武利尤单抗 PD-1抑制剂 治疗22周期 BAL 肺 药物不详，共6个月 不详
男 61 亚洲 转移性非小细胞肺癌 帕博利珠单抗 PD-1抑制剂 治疗2周期 不详 肺 药物不详，共6个月 不详
女 84 亚洲 转移性非小细胞肺癌 纳武利尤单抗 PD-1抑制剂 治疗4周期 不详 肺 不详 不详
Anastasopoulou A等[5] 2019 女 76 高加索 转移性黑色素瘤 纳武利尤单抗 PD-1抑制剂 治疗14周期 BAL、PCR 肺 HRZE（1周） 死亡
Barber DL等[6] 2019 男 59 亚洲 转移性鼻咽癌 纳武利尤单抗 PD-1抑制剂 治疗3周期 组织学、BAL、痰PCR 播散性 1HRZE 死亡
男 83 高加索 默克尔细胞瘤 帕博利珠单抗 PD-1抑制剂 治疗11周期 组织学 肺 HRZE→RO共9月 治愈
Tsai CC等[7] 2019 男 49 亚洲 硬腭鳞状细胞癌 纳武利尤单抗 PD-1抑制剂 治疗6周期 痰培养、抗酸染色 肺 药物不详，共5个月 死亡
Takata S等[8] 2019 男 75 亚洲 转移性非小细胞肺癌 纳武利尤单抗 PD-1抑制剂 治疗15周期 痰涂片抗酸染色、PCR 肺 HRZE 10 d→HEO（不详）→7HR 治愈
Picchi H等[9] 2018 男 50 高加索 转移性黑色素瘤 帕博利珠单抗 PD-1抑制剂 治疗4周期 组织学、PPD 胸膜 HRZE （时间不详） 治愈
男 64 高加索 转移性非小细胞肺癌 纳武利尤单抗 PD-1抑制剂 治疗2周期 组织学、骨培养、PCR 骨 HRZE（时间不详） 死亡
Jensen KH等[10] 2018 男 56 高加索 转移性非小细胞肺癌 纳武利尤单抗 PD-1抑制剂 治疗12周期 组织学、PCR 肺 不详 不详
He W等[11] 2018 女 65 亚洲 转移性黑色素瘤 帕博利珠单抗 PD-1抑制剂 治疗10周期 Xpert、BAL培养 肺 2HRZE→4SEO 治愈
Chu YC等[12] 2017 男 59 亚洲 转移性非小细胞肺癌 纳武利尤单抗 PD-1抑制剂 治疗3周期 组织学、心包液培养 心包 不详 治愈
Fujita K等[13] 2016 男 72 亚洲 转移性非小细胞肺癌 纳武利尤单抗 PD-1抑制剂 治疗8周期 BAL培养、PCR，IGRA 肺 不详 不详
Lee JJ等[14] 2016 男 87 亚洲 霍奇金淋巴瘤 纳武利尤单抗 PD-1抑制剂 治疗5周期 痰培养 肺 HRE（时间不详） 治愈
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