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肝细胞癌免疫微环境中的T淋巴细胞:对人类免疫学和免疫治疗的见解

T lymphocytes in hepatocellular carcinoma immune microenvironment: insights into human immunology and immunotherapy.

作者信息

Bian Jin, Lin Jianzhen, Long Junyu, Yang Xu, Yang Xiaobo, Lu Xin, Sang Xinting, Zhao Haitao

机构信息

Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC) Beijing, China.

Pancreas Center, First Affiliated Hospital of Nanjing Medical University Nanjing, China.

出版信息

Am J Cancer Res. 2020 Dec 1;10(12):4585-4606. eCollection 2020.

Abstract

Hepatocellular carcinoma (HCC) is characterized by poor outcome and shows limited drug-response in clinical trials. Tumor immune microenvironment (TIME) exerts a strong selection pressure on HCC, leading to HCC evolvement and recurrence after multiple therapies. T cell-mediated immunoreaction during cancer surveillance and clearance is central in cancer immunity. Heterogenous T cell subsets play multiple roles in HCC development and progression. The re-educated T cells in TIME usually lead to deteriorated T cell response and tumor progression. Investigation into immune system dysregulation during HCC development will shed light on how to turn immune suppressive state to immune activation and induce more efficient immune response. Emerging T cell-based treatment such as cancer vaccines, CAR-T cell therapy, adoptive cell therapy, and immune checkpoint inhibitors (ICIs), have been proved to cause tumor regression in some clinical and preclinical trials. In this review, we focused on recent studies that explored T cells involved in HCC and how they affect the course of disease. We also briefly outlined current T cell-based immunotherapies in HCC.

摘要

肝细胞癌(HCC)的特点是预后较差,且在临床试验中显示出有限的药物反应。肿瘤免疫微环境(TIME)对HCC施加强大的选择压力,导致HCC在多次治疗后发生演变和复发。在癌症监测和清除过程中,T细胞介导的免疫反应是癌症免疫的核心。异质性T细胞亚群在HCC的发生和发展中发挥多种作用。TIME中经过重新编程的T细胞通常会导致T细胞反应恶化和肿瘤进展。对HCC发生过程中免疫系统失调的研究将有助于揭示如何将免疫抑制状态转变为免疫激活状态,并诱导更有效的免疫反应。新兴的基于T细胞的治疗方法,如癌症疫苗、嵌合抗原受体T细胞(CAR-T)疗法、过继性细胞疗法和免疫检查点抑制剂(ICIs),已在一些临床和临床前试验中被证明可导致肿瘤消退。在本综述中,我们重点关注了探索参与HCC的T细胞及其如何影响疾病进程的最新研究。我们还简要概述了目前用于HCC的基于T细胞的免疫疗法。

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