Immunotherapy for hepatocellular carcinoma

IF 9.5 1区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY JHEP Reports Pub Date : 2024-06-09 DOI:10.1016/j.jhepr.2024.101130
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Abstract

Hepatocellular carcinoma (HCC) is a major global healthcare challenge, with >1 million patients predicted to be affected annually by 2025. In contrast to other cancers, both incidence and mortality rates continue to rise, and HCC is now the third leading cause of cancer-related death worldwide. Immune checkpoint inhibitors (ICIs) have transformed the treatment landscape for advanced HCC, with trials demonstrating a superior overall survival benefit compared to sorafenib in the first-line setting. Combination therapy with either atezolizumab (anti-PD-L1) and bevacizumab (anti-VEGF) or durvalumab (anti-PD-L1) and tremelimumab (anti-CTLA-4) is now recognised as standard of care for advanced HCC. More recently, two phase III studies of ICI-based combination therapy in the early and intermediate disease settings have successfully met their primary end points of improved recurrence- and progression-free survival, respectively. Despite these advances, and in contrast to other tumour types, there remain no validated predictive biomarkers of response to ICIs in HCC. Ongoing research efforts are focused on further characterising the tumour microenvironment in order to select patients most likely to benefit from ICI and identify novel therapeutic targets. Herein, we review the current understanding of the immune landscape in which HCC develops and the evidence for ICI-based therapeutic strategies in HCC. Additionally, we describe the state of biomarker development and novel immunotherapy approaches in HCC which have progressed beyond the pre-clinical stage and into early-phase trials.

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肝细胞癌的免疫疗法
肝细胞癌(HCC)是全球医疗保健领域的一大挑战,预计到 2025 年,每年将有 100 万患者受到影响。与其他癌症相比,HCC 的发病率和死亡率都在持续上升,目前已成为全球癌症相关死亡的第三大原因。免疫检查点抑制剂(ICIs)改变了晚期HCC的治疗格局,试验表明,在一线治疗中,ICIs的总生存期优于索拉非尼。atezolizumab(抗PD-L1)和贝伐单抗(抗VEGF)或durvalumab(抗PD-L1)和tremelimumab(抗CTLA-4)的联合疗法现已被公认为晚期HCC的标准疗法。最近,两项基于 ICI 的早期和中期联合疗法 III 期研究分别成功达到了改善复发和无进展生存期的主要终点。尽管取得了这些进展,但与其他肿瘤类型不同的是,目前仍没有有效的生物标志物来预测 HCC 对 ICIs 的反应。目前的研究工作主要集中在进一步确定肿瘤微环境的特征,以便选择最有可能从 ICI 中获益的患者,并确定新的治疗靶点。在此,我们回顾了目前对 HCC 发病免疫环境的理解,以及基于 ICI 的 HCC 治疗策略的证据。此外,我们还介绍了 HCC 的生物标记物开发和新型免疫疗法方法的现状,这些方法已经超越了临床前阶段,进入了早期试验阶段。
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来源期刊
JHEP Reports
JHEP Reports GASTROENTEROLOGY & HEPATOLOGY-
CiteScore
12.40
自引率
2.40%
发文量
161
审稿时长
36 days
期刊介绍: JHEP Reports is an open access journal that is affiliated with the European Association for the Study of the Liver (EASL). It serves as a companion journal to the highly respected Journal of Hepatology. The primary objective of JHEP Reports is to publish original papers and reviews that contribute to the advancement of knowledge in the field of liver diseases. The journal covers a wide range of topics, including basic, translational, and clinical research. It also focuses on global issues in hepatology, with particular emphasis on areas such as clinical trials, novel diagnostics, precision medicine and therapeutics, cancer research, cellular and molecular studies, artificial intelligence, microbiome research, epidemiology, and cutting-edge technologies. In summary, JHEP Reports is dedicated to promoting scientific discoveries and innovations in liver diseases through the publication of high-quality research papers and reviews covering various aspects of hepatology.
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Contents Editorial Board page Copyright and information Contents ALT levels, alcohol use, and metabolic risk factors have prognostic relevance for liver-related outcomes in the general population
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