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肝细胞癌的免疫微环境:从发病机制到免疫治疗

英文原题:Immune microenvironment in hepatocellular carcinoma: from pathogenesis to immunotherapy.

PubMed 2025/06/11(内容时间) Cell Mol Immunol Q1 · IF 23.9(JCR 2025)

研究概要

肝细胞癌(HCC)是一种日益普遍且致命的疾病,由多种病因因素引发,如酒精相关性肝病(ALD)、代谢功能障碍相关脂肪性肝炎(MASH)、病毒性肝炎以及其他肝毒性和肝癌源性因素。

中文摘要

肝细胞癌(HCC)是一种日益普遍且致命的疾病,由多种病因因素引发,如酒精相关性肝病(ALD)、代谢功能障碍相关脂肪性肝炎(MASH)、病毒性肝炎以及其他肝毒性和肝癌源性因素。HCC的肿瘤微环境(TME)以多种不同的成纤维细胞和免疫细胞类型为特征,这些细胞均影响这种恶性肿瘤的发生、进展和转移。这种复杂的免疫TME可分为固有免疫组分,包括巨噬细胞、中性粒细胞、树突状细胞、髓源性抑制细胞、黏膜相关恒定T细胞、NK 细胞、自然杀伤T细胞和固有淋巴细胞,以及适应性免疫组分,包括CD4+ T细胞、CD8+ T细胞、调节性T细胞和B细胞。在本综述中,我们讨论了揭示这些免疫细胞(以及肝星状细胞等成纤维样细胞)在HCC发病机制中直接或间接作用的最新发现。今后,进一步表征这种异质性TME对于研究HCC的进展和开发新型免疫治疗选择至关重要。与此相应,我们还综述了旨在专门阐明这一复杂TME的新型突破性实验技术和动物模型,并讨论了旨在治疗HCC和预测这些免疫疗法疗效的新兴免疫治疗策略。

展开英文摘要原文

Hepatocellular carcinoma (HCC) is an increasingly prevalent and deadly disease that is initiated by different etiological factors, such as alcohol-associated liver disease (ALD), metabolic dysfunction-associated steatohepatitis (MASH), viral hepatitis, and other hepatotoxic and hepatocarcinogenic agents. The tumor microenvironment (TME) of HCC is characterized by several different fibroblastic and immune cell types, all of which affect the initiation, progression and metastasis of this malignant cancer. This complex immune TME can be divided into an innate component that includes macrophages, neutrophils, dendritic cells, myeloid-derived suppressor cells, mucosal-associated invariant T cells, natural killer cells, natural killer T cells, and innate lymphoid cells, as well as an adaptive component that includes CD4 + T cells, CD8 + T cells, regulatory T cells, and B cells. In this review, we discuss the latest findings shedding light on the direct or indirect roles of these immune cells (and fibroblastic-like cells such as hepatic stellate cells) in the pathogenesis of HCC. Henceforth, further characterization of this heterogeneous TME is highly important for studying the progression of HCC and developing novel immunotherapeutic treatment options. In line with this, we also review novel groundbreaking experimental techniques and animal models aimed at specifically elucidating this complex TME and discuss emerging immune-based therapeutic strategies intended to treat HCC and predict the efficacy of these immunotherapies.

论文信息

作者
Seyhan D、Allaire M、Fu Y、Conti F、Wang XW、Gao B、Lafdil F
第一作者单位
Doctoral School of "Physiologie, Physiopathologie & Thérapeutique", Sorbonne Université, Paris, France.Germany
通讯作者单位
Université Paris-Est Créteil (UPEC), Créteil, France. fouad.lafdil@u-pec.fr.France
文献类型
综述 · 非美国政府资助研究 · 美国 NIH 院内研究
期刊
Cellular & molecular immunology2025 Oct
原文标识
PubMed 40500404 · DOI 10.1038/s41423-025-01308-4