Papadopoulos Grigorios, Giannousi Eirini, Avdi Aikaterini P, Velliou Rallia-Iliana, Nikolakopoulou Polyxeni, Chatzigeorgiou Antonios
Department of Physiology, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
Department of Neuroscience, Karolinska Institute, Stockholm, Sweden.
Front Cell Dev Biol. 2024 May 7;12:1343806. doi: 10.3389/fcell.2024.1343806. eCollection 2024.
Metabolic dysfunction-associated steatohepatitis (MASH) is the progressed version of metabolic dysfunction-associated steatotic liver disease (MASLD) characterized by inflammation and fibrosis, but also a pathophysiological "hub" that favors the emergence of liver malignancies. Current research efforts aim to identify risk factors, discover disease biomarkers, and aid patient stratification in the context of MASH-induced hepatocellular carcinoma (HCC), the most prevalent cancer among MASLD patients. To investigate the tumorigenic transition in MASH-induced HCC, researchers predominantly exploit preclinical animal-based MASH models and studies based on archived human biopsies and clinical trials. Recapitulating the immune response during tumor development and progression is vital to obtain mechanistic insights into MASH-induced HCC. Notably, the advanced complexity behind MASLD and MASH pathogenesis shifted the research focus towards innate immunity, a fundamental element of the hepatic immune niche that is usually altered robustly in the course of liver disease. During the last few years, however, there has been an increasing interest for deciphering the role of adaptive immunity in MASH-induced HCC, particularly regarding the functions of the various T cell populations. To effectively understand the specific role of T cells in MASH-induced HCC development, scientists should urgently fill the current knowledge gaps in this field. Pinpointing the metabolic signature, sketching the immune landscape, and characterizing the cellular interactions and dynamics of the specific T cells within the MASH-HCC liver are essential to unravel the mechanisms that adaptive immunity exploits to enable the emergence and progression of this cancer. To this end, our review aims to summarize the current state of research regarding the T cell functions linked to MASH-induced HCC.
代谢功能障碍相关脂肪性肝炎（MASH）是代谢功能障碍相关脂肪性肝病（MASLD）的进展形式，其特征为炎症和纤维化，也是肝脏恶性肿瘤发生的病理生理“枢纽”。目前的研究致力于识别风险因素、发现疾病生物标志物，并在MASH诱发的肝细胞癌（HCC）（MASLD患者中最常见的癌症）背景下辅助患者分层。为了研究MASH诱发的HCC中的肿瘤发生转变，研究人员主要利用基于临床前动物的MASH模型以及基于存档人类活检和临床试验的研究。在肿瘤发生和进展过程中重现免疫反应对于深入了解MASH诱发的HCC的机制至关重要。值得注意的是，MASLD和MASH发病机制背后的高度复杂性将研究重点转向了固有免疫，这是肝脏免疫微环境的一个基本要素，在肝病过程中通常会发生显著改变。然而，在过去几年中，人们对破译适应性免疫在MASH诱发的HCC中的作用越来越感兴趣，特别是关于各种T细胞群体的功能。为了有效理解T细胞在MASH诱发的HCC发展中的具体作用，科学家们应迫切填补该领域当前的知识空白。明确代谢特征、勾勒免疫格局以及表征MASH-HCC肝脏内特定T细胞的细胞间相互作用和动态，对于揭示适应性免疫促使这种癌症发生和进展的机制至关重要。为此，我们的综述旨在总结与MASH诱发的HCC相关的T细胞功能的当前研究状况。
