Immune checkpoints in hepatocellular carcinoma and the challenges of therapeutic resistance.

IF 3 4区医学 Q3 IMMUNOLOGY

Immunopharmacology and Immunotoxicology Pub Date : 2025-10-01 Epub Date: 2025-08-31 DOI:10.1080/08923973.2025.2542137

Xin Tao, Xiaoxia Yang

{"title":"Immune checkpoints in hepatocellular carcinoma and the challenges of therapeutic resistance.","authors":"Xin Tao, Xiaoxia Yang","doi":"10.1080/08923973.2025.2542137","DOIUrl":null,"url":null,"abstract":"Objective: Immune checkpoint inhibitors (ICIs) made a big change in the treatment of hepatocellular carcinoma (HCC), thereby bringing fresh hope in terms of treatment to patients with few options until that time.Methods: However, ICIs still encounter resistance mechanisms in a substantial number of patients, either in primary or secondary forms. This phenomenon of resistance occurs due to various reasons that comprise but are not restricted to epigenetic alterations, immunosuppressive tumor microenvironments, and activation of TGF-β and VEGF signaling pathways.Results: In this study, we will discuss the mechanisms of ICI resistance in HCC and these emerging avenues of therapy as an approach to circumvent the resistance. The rationale and current status of ongoing trials to combine ICIs with anti-angiogenic agents, epigenetic modulating agents, and local therapies will be discussed.Discussion: In a nutshell, we indicate an immediate need for reliable predictive biomarkers and personalized treatment approaches to improve clinical outcomes. Therefore, by managing challenges and knowledge gaps, this review presents a futurist outlook while charting a course for subsequent clinical trials designed to optimize immunotherapeutic results in HCC.","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":" ","pages":"666-686"},"PeriodicalIF":3.0000,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Immunopharmacology and Immunotoxicology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/08923973.2025.2542137","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/8/31 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"IMMUNOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Objective: Immune checkpoint inhibitors (ICIs) made a big change in the treatment of hepatocellular carcinoma (HCC), thereby bringing fresh hope in terms of treatment to patients with few options until that time.

Methods: However, ICIs still encounter resistance mechanisms in a substantial number of patients, either in primary or secondary forms. This phenomenon of resistance occurs due to various reasons that comprise but are not restricted to epigenetic alterations, immunosuppressive tumor microenvironments, and activation of TGF-β and VEGF signaling pathways.

Results: In this study, we will discuss the mechanisms of ICI resistance in HCC and these emerging avenues of therapy as an approach to circumvent the resistance. The rationale and current status of ongoing trials to combine ICIs with anti-angiogenic agents, epigenetic modulating agents, and local therapies will be discussed.

Discussion: In a nutshell, we indicate an immediate need for reliable predictive biomarkers and personalized treatment approaches to improve clinical outcomes. Therefore, by managing challenges and knowledge gaps, this review presents a futurist outlook while charting a course for subsequent clinical trials designed to optimize immunotherapeutic results in HCC.

查看原文本刊更多论文

肝细胞癌的免疫检查点和治疗耐药性的挑战。

目的：免疫检查点抑制剂（ICIs）对肝细胞癌（HCC）的治疗产生了巨大的改变，从而为那些在此之前选择不多的患者带来了新的治疗希望。方法：然而，在相当数量的患者中，无论是原发性还是继发性，ICIs仍然遇到耐药机制。这种耐药现象的发生有多种原因，包括但不限于表观遗传改变、免疫抑制肿瘤微环境以及TGF-β和VEGF信号通路的激活。结果：在本研究中，我们将讨论HCC中ICI耐药的机制，以及这些新兴的治疗途径作为规避耐药的方法。将讨论正在进行的将ICIs与抗血管生成药物、表观遗传调节剂和局部治疗相结合的试验的基本原理和现状。讨论：简而言之，我们认为迫切需要可靠的预测性生物标志物和个性化治疗方法来改善临床结果。因此，通过管理挑战和知识差距，本综述提出了未来的展望，同时为后续临床试验绘制了路线图，旨在优化HCC的免疫治疗结果。

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

Immunopharmacology and Immunotoxicology 医学-毒理学

CiteScore

5.40

自引率

0.00%

发文量

133

审稿时长

4-8 weeks

期刊介绍： The journal Immunopharmacology and Immunotoxicology is devoted to pre-clinical and clinical drug discovery and development targeting the immune system. Research related to the immunoregulatory effects of various compounds, including small-molecule drugs and biologics, on immunocompetent cells and immune responses, as well as the immunotoxicity exerted by xenobiotics and drugs. Only research that describe the mechanisms of specific compounds (not extracts) is of interest to the journal. The journal will prioritise preclinical and clinical studies on immunotherapy of disorders such as chronic inflammation, allergy, autoimmunity, cancer etc. The effects of small-drugs, vaccines and biologics against central immunological targets as well as cell-based therapy, including dendritic cell therapy, T cell adoptive transfer and stem cell therapy, are topics of particular interest. Publications pointing towards potential new drug targets within the immune system or novel technology for immunopharmacological drug development are also welcome. With an immunoscience focus on drug development, immunotherapy and toxicology, the journal will cover areas such as infection, allergy, inflammation, tumor immunology, degenerative disorders, immunodeficiencies, neurology, atherosclerosis and more. Immunopharmacology and Immunotoxicology will accept original manuscripts, brief communications, commentaries, mini-reviews, reviews, clinical trials and clinical cases, on the condition that the results reported are based on original, clinical, or basic research that has not been published elsewhere in any journal in any language (except in abstract form relating to paper communicated to scientific meetings and symposiums).