免疫检查点抑制剂在肝细胞癌治疗中的应用:耐药机制、肝移植挑战和管理策略。

IF 4.6 Q1 ONCOLOGY
癌症耐药(英文) Pub Date : 2025-09-11 eCollection Date: 2025-01-01 DOI:10.20517/cdr.2025.120
Yutao Chen, Desheng Chen, Zhixing Liang, Haoyuan Yu, Haobin Sun, Yongwei Hu, Peng Jiang, Mingshen Zhang, Linsen Ye, Hua Li
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引用次数: 0

摘要

肝细胞癌(HCC)由于其侵袭性、肿瘤异质性和有限的治疗效果,给临床带来了巨大的负担。虽然免疫检查点抑制剂(ICIs)已经彻底改变了治疗模式,并显示出相当大的前景,但耐药机制的出现对当代临床肿瘤学提出了严峻的挑战。新型药物和创新联合策略的加速发展使这种耐药性格局进一步复杂化。在这篇综述中,我们通过整合对原发性耐药、获得性耐药和宿主相关因素的见解,对HCC中的ICI耐药机制进行了独特而全面的分析。在这一机制框架的基础上,我们探索了克服ICI耐药性的新兴治疗策略。此外,我们评估了ICIs在HCC治疗中的双重作用——作为移植候选人的新辅助治疗,同时也带来了移植后排斥反应的风险。通过将临床前发现与临床现实联系起来,本分析旨在为HCC患者提供合理的治疗设计和优化免疫肿瘤学试验。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Immune checkpoint inhibitors in hepatocellular carcinoma therapy: resistance mechanisms, liver transplantation challenges and management strategies.

Immune checkpoint inhibitors in hepatocellular carcinoma therapy: resistance mechanisms, liver transplantation challenges and management strategies.

Immune checkpoint inhibitors in hepatocellular carcinoma therapy: resistance mechanisms, liver transplantation challenges and management strategies.

Hepatocellular carcinoma (HCC) poses a significant clinical burden due to its aggressive nature, profound tumor heterogeneity, and limited therapeutic efficacy. While immune checkpoint inhibitors (ICIs) have revolutionized treatment paradigms and demonstrated considerable promise, the emergence of resistance mechanisms has posed a critical challenge in contemporary clinical oncology. The accelerated development of novel agents and innovative combination strategies has further complicated this resistance landscape. In this review, we present a unique and comprehensive analysis of ICI resistance mechanisms in HCC by integrating insights into primary resistance, acquired resistance, and host-related factors. Building upon this mechanistic framework, we explore emerging therapeutic strategies to overcome ICI resistance. Furthermore, we evaluate the dual role of ICIs in HCC management - serving as a neoadjuvant therapy for transplant candidates while simultaneously posing risks of post-transplant rejection. By bridging preclinical discoveries with clinical realities, this analysis aims to inform rational therapeutic design and optimize immuno-oncology trials for HCC patients.

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