The immune microenvironment of steatotic hepatocellular carcinoma: Current findings and future prospects.

IF 5.6 2区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY
Hepatology Communications Pub Date : 2024-09-03 eCollection Date: 2024-09-01 DOI:10.1097/HC9.0000000000000516
Jacinth Wing-Sum Cheu, Carmen Chak-Lui Wong
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引用次数: 0

Abstract

Hepatocellular carcinoma (HCC), the major type of primary liver cancer, is notorious for its resistance to systemic treatments. The field has made a great leap in the past decade, with the number of FDA-approved therapies for advanced HCC increasing from 1 to 9. Although tyrosine kinase inhibitors remain the most common first-line option as monotherapy treatment, the clinical success of immune checkpoint inhibitors, especially when used in combination with anti-VEGF/VEGFR in HCC will likely transform the treatment landscape. While immune checkpoint inhibitors represent an exciting therapeutic revenue for HCC, recent studies have revealed that nonviral HCC, which is primarily caused by metabolic dysfunction-associated steatotic hepatitis (MASH), has a distinct and less favorable response to the immune checkpoint inhibitors. MASH is the most rapidly increasing etiology for HCC. The immune microenvironment of MASH-HCC is greatly affected by the intertwined pathological processes of steatosis-induced iterative cycles between steatohepatitis and liver injury. Here, we present a timely summary of the immune microenvironment of MASH-HCC. We will delve into the use of cutting-edge technologies, such as single-cell RNA sequencing, spatial transcriptomics, and mass cytometry imaging, to deconvolute the complexity of the immune ecosystem in MASH-HCC. We will also discuss the novel therapeutic innovations for MASH-HCC in preclinical models, such as the metabolic inhibitor, epigenetic inhibitor, and immunomodulator. These inhibitors all have the ability to subvert the immune microenvironment of MASH-HCC, improving the efficiency of anti-PD-1. While awaiting new drugs to be tested in clinical trials, the knowledge gained from these investigations is crucial for the development of personalized and effective treatment strategies for MASH-HCC.

脂肪性肝细胞癌的免疫微环境:当前发现与未来展望。
肝细胞癌(HCC)是原发性肝癌的主要类型,因其对全身治疗的耐药性而臭名昭著。在过去的十年中,这一领域取得了巨大的飞跃,FDA 批准的晚期 HCC 治疗方法从 1 种增加到 9 种。尽管酪氨酸激酶抑制剂仍是最常见的一线单药治疗选择,但免疫检查点抑制剂的临床成功,尤其是与抗血管内皮生长因子/血管内皮生长因子受体联合用于治疗 HCC 时,很可能会改变治疗格局。虽然免疫检查点抑制剂是治疗 HCC 的一项令人兴奋的收入,但最近的研究发现,主要由代谢功能障碍相关性脂肪性肝炎(MASH)引起的非病毒性 HCC 对免疫检查点抑制剂的反应截然不同,而且反应较差。MASH是HCC发病率增长最快的病因。脂肪性肝炎和肝损伤交织循环的病理过程极大地影响了 MASH-HCC 的免疫微环境。在此,我们将及时总结 MASH-HCC 的免疫微环境。我们将深入探讨单细胞 RNA 测序、空间转录组学和质谱成像等前沿技术的应用,以揭示 MASH-HCC 免疫生态系统的复杂性。我们还将讨论临床前模型中针对 MASH-HCC 的新型创新疗法,如代谢抑制剂、表观遗传抑制剂和免疫调节剂。这些抑制剂都能颠覆MASH-HCC的免疫微环境,提高抗PD-1的效率。在等待新药进行临床试验的同时,从这些研究中获得的知识对于开发个性化和有效的 MASH-HCC 治疗策略至关重要。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Hepatology Communications
Hepatology Communications GASTROENTEROLOGY & HEPATOLOGY-
CiteScore
8.00
自引率
2.00%
发文量
248
审稿时长
8 weeks
期刊介绍: Hepatology Communications is a peer-reviewed, online-only, open access journal for fast dissemination of high quality basic, translational, and clinical research in hepatology. Hepatology Communications maintains high standard and rigorous peer review. Because of its open access nature, authors retain the copyright to their works, all articles are immediately available and free to read and share, and it is fully compliant with funder and institutional mandates. The journal is committed to fast publication and author satisfaction. ​
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