In association with the pandemic spreading of obesity and metabolic syndrome, the prevalence of NAFLD-related HCC is increasing almost exponentially. In recent years, many of the underlining multifactorial causes of NAFLD have been identified, and the cellular mechanisms sustaining disease development have been dissected up to the single-cell level. However, there is still an urgent need to provide clinicians with more therapeutic targets, with particular attention on NAFLD-induced HCC, where immune checkpoint inhibitors do not work as efficiently. Whereas much effort has been invested in elucidating the role of innate immune response in the hepatic NAFLD microenvironment, only in the past decade have novel critical roles been unraveled for T cells in driving chronic inflammation toward HCC. The metabolic and immune microenvironment interact to recreate a tumor-promoting and immune-suppressive terrain, responsible for resistance to anticancer therapy. In this article, we will review the specific functions of several T-cell populations involved in NAFLD and NAFLD-driven HCC. We will illustrate the cellular crosstalk with other immune cells, regulatory networks or stimulatory effects of these interactions, and role of the metabolic microenvironment in influencing immune cell functionality. Finally, we will present the pros and cons of the current therapeutic strategies against NAFLD-related HCC and delineate possible novel approaches for the future.

中文翻译：

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T 细胞：NASH 发病机制和肝癌发生中的朋友和敌人

与肥胖和代谢综合征的大流行相关，NAFLD 相关 HCC 的患病率几乎呈指数增长。近年来，已经确定了 NAFLD 的许多重要的多因素原因，并且已经对维持疾病发展的细胞机制进行了单细胞水平的剖析。然而，仍然迫切需要为临床医生提供更多的治疗靶点，尤其是免疫检查点抑制剂无法有效发挥作用的 NAFLD 诱发的 HCC。尽管已经投入了大量精力来阐明先天免疫反应在肝脏 NAFLD 微环境中的作用，但仅在过去十年中，T 细胞在推动慢性炎症向 HCC 发展中的新关键作用才得到阐明。代谢和免疫微环境相互作用以重建肿瘤促进和免疫抑制地形，负责对抗癌治疗的抵抗力。在这篇文章中，我们将回顾几个参与 NAFLD 和 NAFLD 驱动的 HCC 的 T 细胞群的具体功能。我们将说明与其他免疫细胞的细胞串扰、调节网络或这些相互作用的刺激作用，以及代谢微环境在影响免疫细胞功能中的作用。最后，我们将介绍当前针对 NAFLD 相关 HCC 的治疗策略的优缺点，并描述未来可能的新方法。我们将回顾涉及 NAFLD 和 NAFLD 驱动的 HCC 的几个 T 细胞群的具体功能。我们将说明与其他免疫细胞的细胞串扰、调节网络或这些相互作用的刺激作用，以及代谢微环境在影响免疫细胞功能中的作用。最后，我们将介绍当前针对 NAFLD 相关 HCC 的治疗策略的优缺点，并描述未来可能的新方法。我们将回顾涉及 NAFLD 和 NAFLD 驱动的 HCC 的几个 T 细胞群的具体功能。我们将说明与其他免疫细胞的细胞串扰、调节网络或这些相互作用的刺激作用，以及代谢微环境在影响免疫细胞功能中的作用。最后，我们将介绍当前针对 NAFLD 相关 HCC 的治疗策略的优缺点，并描述未来可能的新方法。