抗PD-1 / PD-L1封锁免疫疗法用于治疗乙型肝炎病毒感染相关的

StephenW

Anti-PD-1/PD-L1 Blockade Immunotherapy Employed in Treating Hepatitis B Virus Infection-Related Advanced Hepatocellular Carcinoma: A Literature Review
Bin Li  1 , Cong Yan  1 , Jiamin Zhu  1 , Xiaobing Chen  2 , Qihan Fu  1 , Hangyu Zhang  1 , Zhou Tong  1 , Lulu Liu  1 , Yi Zheng  1 , Peng Zhao  1 , Weiqin Jiang  1 , Weijia Fang  1
Affiliations

    PMID: 32547550 PMCID: PMC7270402 DOI: 10.3389/fimmu.2020.01037

Abstract

Hepatitis B virus (HBV) infection is regarded as the main etiological risk factor in the process of hepatocellular carcinoma (HCC), as it promotes an immunosuppressive microenvironment that is partially mediated by the programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) signaling pathway. The tumor microenvironment (TME) of HBV-related HCC is indeed more immunosuppressive than microenvironments not associated with viruses. And compared to TME in hepatitis C virus (HCV) infected HCC, TME of HBV-related HCC is less vascularized and presents different immune components resulting in similar immunosuppression. However, few studies are focusing on the specific side effects and efficacy of PD-1/PD-L1 blockade immunotherapy in HBV-related HCC patients, as well as on the underlying mechanism. Herein, we reviewed the basic research focusing on potential TME alteration caused by HBV infection, especially in HCC patients. Moreover, we reviewed PD-1/PD-L1 blockade immunotherapy clinical trials to clarify the safety and efficacy of this newly developed treatment in the particular circumstances of HBV infection. We found that patients with HBV-related HCC displayed an acceptable safety profile similar to those of non-infected HCC patients. However, we could not determine the antiviral activity of PD-1/PD-L1 blockade because standard anti-viral therapies were conducted in all of the current clinical trials, which made it difficult to distinguish the potential influence of PD-1/PD-L1 blockade on HBV infection. Generally, the objective response rates (ORRs) of PD-1/PD-L1 blockade immunotherapy did not differ significantly between virus-positive and virus-negative patients, except that disease control rates (DCRs) were obviously lower in HBV-infected HCC patients.

Keywords: hepatitis B virus; hepatocellular carcinoma; immunotherapy; programmed cell death protein 1; programmed death-ligand 1; tumor microenvironment.

Copyright © 2020 Li, Yan, Zhu, Chen, Fu, Zhang, Tong, Liu, Zheng, Zhao, Jiang and Fang.

StephenW

抗PD-1 / PD-L1封锁免疫疗法用于治疗乙型肝炎病毒感染相关的晚期肝细胞癌：文献综述。
李斌1，丛岩1，朱佳敏1，陈小冰2，傅启汉1，张航宇1，周彤1，刘露露1，仪征1，赵鹏1，姜维琴1，魏家坊1
隶属关系

    PMID：32547550 PMCID：PMC7270402 DOI：10.3389 / fimmu.2020.01037

抽象

乙型肝炎病毒（HBV）感染被认为是肝细胞癌（HCC）进程中的主要病因，因为它促进免疫抑制性微环境，该环境部分由程序性细胞死亡蛋白1（PD-1）/程序性死亡介导-配体1（PD-L1）信号通路。 HBV相关HCC的肿瘤微环境（TME）实际上比与病毒无关的微环境具有更高的免疫抑制作用。与丙型肝炎病毒（HCV）感染的HCC中的TME相比，与HBV相关的HCC的TME的血管化程度更低，并且呈现出不同的免疫成分，从而导致相似的免疫抑制。但是，很少有研究关注于HBV相关HCC患者的PD-1 / PD-L1阻断免疫疗法的特定副作用和疗效，以及其潜在机制。本文中，我们回顾了基础研究，重点是由HBV感染引起的潜在TME改变，尤其是在HCC患者中。此外，我们审查了PD-1 / PD-L1封锁免疫疗法的临床试验，以阐明这种新开发的疗法在特定的HBV感染情况下的安全性和有效性。我们发现，与未感染的HCC患者相似，HBV相关的HCC患者显示出可接受的安全性。但是，我们无法确定PD-1 / PD-L1阻滞剂的抗病毒活性，因为在所有当前的临床试验中都进行了标准的抗病毒治疗，这使得难以区分PD-1 / PD-L-的潜在影响L1阻断HBV感染。通常，PD-1 / PD-L1阻断免疫治疗的客观反应率（ORR）在病毒阳性和病毒阴性患者之间没有显着差异，除了在HBV感染的HCC患者中疾病控制率（DCR）明显较低外。

关键词：乙型肝炎病毒；肝细胞癌；免疫疗法程序性细胞死亡蛋白1；程序化死亡配体1；肿瘤微环境。

版权所有©2020 Li，Yan，Zhu，Chen，Fu，Zhang，Tong，Liu，Zheng，Zhao，Jiang and Fang。

StephenW

https://www.frontiersin.org/articles/10.3389/fimmu.2020.01037/pdf