NASH and Hepatocellular Carcinoma: Immunology and Immunotherapy.
NASH and Hepatocellular Carcinoma: Immunology and Immunotherapy.
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DOI：
10.1158/1078-0432.ccr-21-1258
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发表时间：
2023-02-01
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过去十年彻底改变了我们对非酒精性脂肪性肝病和随之而来的肝癌的基本认识。很明显，一些先天性和适应性免疫细胞在引发、维持或加剧非酒精性脂肪性肝炎（NASH）（一种最近被定义为自身攻击性的疾病）方面发挥着重要作用。尽管疾病管理的改进旨在减少纤维化的进展，但 NASH 仍将成为肝细胞癌 (HCC) 的主要原因。临床前研究的初步数据表明，与病毒性肝癌相比，NASH 相关性肝癌的免疫治疗疗效可能会降低；然而，缺乏支持这些发现的临床转化的决定性证据。对 NASH 进展与致癌和治疗耐药之间的联系机制进行全面的临床和免疫学表型分析是预防进展为肝硬化、根据预测的癌症风险改善 NASH 监测和分层并最终提高 NASH-HCC 患者生存率的关键。在这篇综述中，我们总结了 NASH 和 NASH-HCC 领域的最新技术，重点关注免疫生物学。我们讨论了支持 NASH 作为一种免疫学上独特的促肿瘤疾病实体的临床前和临床发现，并探讨了 NASH 相关 HCC 的潜在治疗漏洞领域。
The last 10 years have revolutionized our basic understanding of nonalcoholic fatty liver disease and consequent liver cancer. It has become clear that several innate and adaptive immune cells play an important role in initiating, maintaining, or exacerbating nonalcoholic steatohepatitis (NASH)—a disease that has been recently defined as autoaggressive. Despite improved disease management aimed at reducing the progression of fibrosis, NASH is set to become a leading cause for hepatocellular carcinoma (HCC). Preliminary data from preclinical studies suggest that immunotherapy efficacy may be reduced in NASH-related HCC compared with viral HCC; however, conclusive evidence supporting clinical translation of these findings is lacking. Comprehensive clinical and immunologic phenotyping of mechanisms linking NASH progression with carcinogenesis and therapeutic resistance is key to prevent progression to cirrhosis, improve monitoring and stratification of NASH according to predicted cancer risk, and ultimately increase survival of patients with NASH-HCC. In this review, we summarize the state of the art in the field of NASH and NASH-HCC with focus on immunobiology. We discuss preclinical and clinical findings underpinning NASH as an immunologically distinct pro-tumorigenic disease entity, and explore areas of potential therapeutic vulnerabilities in NASH-associated HCC.