Hepatic Metabolic Signature and Its Association with the Response to Immunotherapy in Hepatocellular Carcinoma.

IF 4.4 Q1 IMMUNOLOGY
ImmunoTargets and Therapy Pub Date : 2025-07-23 eCollection Date: 2025-01-01 DOI:10.2147/ITT.S491464
Hyewon Park, Sowon Park, Kena Park, Sun Young Yim, Ju-Seog Lee, Sung Hwan Lee
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引用次数: 0

Abstract

Introduction: Increased metabolic activity is frequently observed in hepatocellular carcinoma (HCC). However, the impact of this increased metabolic activity on the efficacy of current treatments, such as the combination immunotherapy using atezolizumab and bevacizumab for HCC, remains unknown.

Methods: Gene expression data from mouse livers representing hepatic metabolic activity and HCC patient tumor tissues were used to identify a transcriptomic signature for high metabolic activity in HCC tumors. The hepatic metabolic signature (HMS) was used to categorize HCC patients treated with atezolizumab plus bevacizumab or sorafenib from the IMbrave150 clinical trial into high-or low-metabolic groups, using multiple statistical approaches to evaluate the clinical relevance of the signature.

Results: The study uncovered a robust association between high HMS and poor overall survival in HCC patients across multiple independent cohorts. Notably, high HMS patients in IMbrave150 did not show significant benefit of the atezolizumab-bevacizumab treatment in terms of overall survival or progression-free survival compared to sorafenib monotherapy. Conversely, low HMS patients demonstrated superior overall and progression-free survival outcomes with the combination regimen relative to sorafenib alone. Furthermore, an association between high HMS and features of hepatic stem cells and increased genomic instability was identified.

Conclusion: This study provides compelling evidence that the HMS could be a predictive biomarker to identify potential HCC patients with therapeutic benefits from combination immunotherapy with atezolizumab and bevacizumab. Leveraging such predictive metabolic biomarkers may pave the way for tailored, precision medicine strategies that maximize therapeutic responses and improve outcomes for HCC patients.

肝细胞癌的肝脏代谢特征及其与免疫治疗应答的关系。
导读:在肝细胞癌(HCC)中经常观察到代谢活性增加。然而,这种增加的代谢活性对当前治疗的疗效的影响,如使用atezolizumab和bevacizumab治疗HCC的联合免疫治疗,仍然未知。方法:利用代表肝脏代谢活性的小鼠肝脏和HCC患者肿瘤组织的基因表达数据,鉴定HCC肿瘤中高代谢活性的转录组特征。肝代谢特征(HMS)用于将来自IMbrave150临床试验的atezolizumab联合贝伐单抗或索拉非尼治疗的HCC患者分为高代谢组或低代谢组,使用多种统计学方法评估该特征的临床相关性。结果:该研究在多个独立队列中揭示了HCC患者高HMS和低总生存率之间的强大关联。值得注意的是,与索拉非尼单药治疗相比,IMbrave150中的高HMS患者在总生存期或无进展生存期方面没有显示出阿特唑单抗-贝伐单抗治疗的显著益处。相反,与单独使用索拉非尼相比,低HMS患者在联合治疗方案中表现出更好的总体和无进展生存结果。此外,高HMS与肝干细胞特征和增加的基因组不稳定性之间存在关联。结论:这项研究提供了令人信服的证据,证明HMS可以作为一种预测性生物标志物,用于识别潜在的HCC患者,并从阿特唑单抗和贝伐单抗联合免疫治疗中获益。利用这种可预测的代谢生物标志物可能为量身定制的精准医学策略铺平道路,从而最大化治疗反应并改善HCC患者的预后。
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
CiteScore
16.50
自引率
0.00%
发文量
7
审稿时长
16 weeks
期刊介绍: Immuno Targets and Therapy is an international, peer-reviewed open access journal focusing on the immunological basis of diseases, potential targets for immune based therapy and treatment protocols employed to improve patient management. Basic immunology and physiology of the immune system in health, and disease will be also covered.In addition, the journal will focus on the impact of management programs and new therapeutic agents and protocols on patient perspectives such as quality of life, adherence and satisfaction.
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