Immune Checkpoint Inhibitors in Hepatocellular Cancer: Current Understanding on Mechanisms of Resistance and Biomarkers of Response to Treatment.

Q2 Biochemistry, Genetics and Molecular Biology

Gene expression Pub Date : 2020-06-12 Epub Date: 2020-04-27 DOI:10.3727/105221620X15880179864121

Amblessed E Onuma, Hongji Zhang, Hai Huang, Terence M Williams, Anne Noonan, Allan Tsung

{"title":"Immune Checkpoint Inhibitors in Hepatocellular Cancer: Current Understanding on Mechanisms of Resistance and Biomarkers of Response to Treatment.","authors":"Amblessed E Onuma, Hongji Zhang, Hai Huang, Terence M Williams, Anne Noonan, Allan Tsung","doi":"10.3727/105221620X15880179864121","DOIUrl":null,"url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) is the most common primary liver malignancy worldwide and a leading cause of death worldwide. Its incidence continues to increase in the US due to hepatitis C infection and nonalcoholic steatohepatitis. Liver transplantation and resection remain the best therapeutic options for cure, but these are limited by the shortage of available organs for transplantation, diagnosis at advanced stage, and underlying chronic liver disease found in most patients with HCC. Immune checkpoint inhibitors (ICIs) have been shown to be an evolving novel treatment option in certain advanced solid tumors and have been recently approved for inoperable, advanced, and metastatic HCC. Unfortunately, a large cohort of patients with HCC fail to respond to immunotherapy. In this review, we discuss the ICIs currently approved for HCC treatment and their various mechanisms of action. We will highlight current understanding of mechanism of resistance and limitations to ICIs. Finally, we will describe emerging biomarkers of response to ICIs and address future direction on overcoming resistance to immune checkpoint therapy.</p>","PeriodicalId":12502,"journal":{"name":"Gene expression","volume":" ","pages":"53-65"},"PeriodicalIF":0.0000,"publicationDate":"2020-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7284108/pdf/GE-20-53.pdf","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Gene expression","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.3727/105221620X15880179864121","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2020/4/27 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"Biochemistry, Genetics and Molecular Biology","Score":null,"Total":0}

引用次数: 0

Abstract

Hepatocellular carcinoma (HCC) is the most common primary liver malignancy worldwide and a leading cause of death worldwide. Its incidence continues to increase in the US due to hepatitis C infection and nonalcoholic steatohepatitis. Liver transplantation and resection remain the best therapeutic options for cure, but these are limited by the shortage of available organs for transplantation, diagnosis at advanced stage, and underlying chronic liver disease found in most patients with HCC. Immune checkpoint inhibitors (ICIs) have been shown to be an evolving novel treatment option in certain advanced solid tumors and have been recently approved for inoperable, advanced, and metastatic HCC. Unfortunately, a large cohort of patients with HCC fail to respond to immunotherapy. In this review, we discuss the ICIs currently approved for HCC treatment and their various mechanisms of action. We will highlight current understanding of mechanism of resistance and limitations to ICIs. Finally, we will describe emerging biomarkers of response to ICIs and address future direction on overcoming resistance to immune checkpoint therapy.

查看原文本刊更多论文

肝细胞癌中的免疫检查点抑制剂：目前对抗药性机制和治疗反应生物标志物的理解。

肝细胞癌（HCC）是全球最常见的原发性肝脏恶性肿瘤，也是全球死亡的主要原因之一。在美国，由于丙型肝炎感染和非酒精性脂肪性肝炎，其发病率持续上升。肝移植和切除术仍是治愈的最佳治疗方案，但由于可供移植的器官短缺、诊断处于晚期以及大多数 HCC 患者存在潜在的慢性肝病，这些治疗方案受到了限制。在某些晚期实体瘤中，免疫检查点抑制剂（ICIs）已被证明是一种不断发展的新型治疗方案，最近已被批准用于无法手术的晚期和转移性 HCC。不幸的是，大量 HCC 患者对免疫疗法无效。在本综述中，我们将讨论目前获准用于治疗 HCC 的 ICIs 及其各种作用机制。我们将重点介绍目前对 ICIs 耐药机制和局限性的理解。最后，我们将介绍对 ICIs 反应的新兴生物标志物，并探讨克服免疫检查点疗法耐药性的未来方向。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Gene expression 生物-生物工程与应用微生物

CiteScore

3.80

自引率

0.00%

发文量

审稿时长

>12 weeks

期刊介绍： Gene Expression, The Journal of Liver Research will publish articles in all aspects of hepatology. Hepatology, as a research discipline, has seen unprecedented growth especially in the cellular and molecular mechanisms of hepatic health and disease, which continues to have a major impact on understanding liver development, stem cells, carcinogenesis, tissue engineering, injury, repair, regeneration, immunology, metabolism, fibrosis, and transplantation. Continued research and improved understanding in these areas will have a meaningful impact on liver disease prevention, diagnosis, and treatment. The existing journal Gene Expression has expanded its focus to become Gene Expression, The Journal of Liver Research to meet this growing demand. In its revised and expanded scope, the journal will publish high-impact original articles, reviews, short but complete articles, and special articles (editorials, commentaries, opinions) on all aspects of hepatology, making it a unique and invaluable resource for readers interested in this field. The expanded team, led by an Editor-in-Chief who is uniquely qualified and a renowned expert, along with a dynamic and functional editorial board, is determined to make this a premier journal in the field of hepatology.