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肿瘤相关巨噬细胞和 CD8+ T 细胞:HBV 相关 HCC 发病机制中的双重角色

英文原题:Tumor-associated macrophages and CD8+ T cells: dual players in the pathogenesis of HBV-related HCC.

查看英文原题

Tumor-associated macrophages and CD8+ T cells: dual players in the pathogenesis of HBV-related HCC.

PubMed 2024/10/10(内容时间) Front Immunol Q1 · IF 7(JCR 2025)

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中文摘要

HBV感染是肝细胞癌(HCC)发生和发展的关键风险因素,HCC是一种高度侵袭性的肿瘤,其特征是持续存在的免疫抑制微环境。本综述深入分析了HBV相关HCC,并探讨了中性粒细胞、NK 细胞和树突状细胞之间的相互作用,审视了它们在调节肿瘤相关巨噬细胞和CD8+ T细胞以及塑造肿瘤微环境中的作用。CD8+ T细胞和肿瘤相关巨噬细胞(TAMs)是HBV相关HCC免疫抑制微环境中的两个关键角色。

本研究探讨了TAMs最初被招募以对抗感染,随后如何转变,获得促肿瘤表型,转而对抗机体,促进肿瘤细胞增殖,抑制抗肿瘤免疫,并协助癌症扩散。与此同时,CD8+ T细胞对于控制HBV感染至关重要,但在持续慢性病毒炎症的刺激下变得功能失调和耗竭。本综述随后剖析了TAMs如何操纵这种免疫反应,通过精氨酸剥夺等机制进一步耗竭CD8+ T细胞功能,并创造导致耗竭的缺氧环境。

最后,本综述探讨了靶向TAMs和CD8+ T细胞的挑战和有前景的治疗途径,无论是单独靶向还是与抗病毒治疗和个性化医疗方法相结合,为改善HBV相关HCC的预后带来了希望。

展开英文摘要原文

HBV infection is a key risk factor for the development and progression of hepatocellular carcinoma (HCC), a highly invasive tumor, and is characterized by its persistent immunosuppressive microenvironment. This review provides an in-depth analysis of HBV-related HCC and explores the interactions between neutrophils, natural killer cells, and dendritic cells, examining their roles in regulating tumor-associated macrophages and CD8+ T cells and shaping the tumor microenvironment. Two critical players in the immunosuppressive milieu of HBV-related HCC are CD8+ T cells and tumor-associated macrophages (TAMs).

The study explores how TAMs, initially recruited to combat infection, transform, adopting a tumor-promoting phenotype, turning against the body, promoting tumor cell proliferation, suppressing anti-tumor immunity, and assisting in the spread of cancer.

Meanwhile, CD8+ T cells, crucial for controlling HBV infection, become dysfunctional and exhausted in response to persistent chronic viral inflammation. The review then dissects how TAMs manipulate this immune response, further depleting CD8+ T cell functions through mechanisms like arginine deprivation and creating hypoxic environments that lead to exhaustion.

Finally, it explores the challenges and promising therapeutic avenues that target TAMs and CD8+ T cells, either separately or in combination with antiviral therapy and personalized medicine approaches, offering hope for improved outcomes in HBV-related HCC.

论文信息

作者
Khan MN、Mao B、Hu J、Shi M、Wang S、Rehman AU、Li X
单位
Clinical Molecular Medicine Testing Center, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.China
文献类型
综述
期刊
Frontiers in immunology2024
原文标识
PubMed 39450177 · DOI 10.3389/fimmu.2024.1472430