Role of immune cell homeostasis in research and treatment response in hepatocellular carcinoma.

IF 3.2 4区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Clinical and Experimental Medicine Pub Date : 2025-01-18 DOI:10.1007/s10238-024-01543-5
Weihua Song, Meng Li, Wangrui Liu, Wenhao Xu, Hongyun Zhou, Shiyin Wei, Jiachang Chi
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Abstract

Introduction Recently, immune cells within the tumor microenvironment (TME) have become crucial in regulating cancer progression and treatment responses. The dynamic interactions between tumors and immune cells are emerging as a promising strategy to activate the host's immune system against various cancers. The development and progression of hepatocellular carcinoma (HCC) involve complex biological processes, with the role of the TME and tumor phenotypes still not fully understood. Therefore, it is essential to investigate the importance of immune cell homeostasis in HCC. Additionally, understanding the molecular mechanisms and biological functions underlying tumor-immune cell interactions is increasingly recognized as vital for improving therapeutic outcomes in clinical settings. Methods A total of 790 HCC samples were selected from public databases and real-world independent clinical cohorts. Machine learning methods, focusing on immune-related indicators, were applied to these samples. The Boruta algorithm was employed to develop an ICI score, which was used to assess patient prognosis and predict responses to immunotherapy. Additionally, a new immune subtype analysis of HCC was performed. Cellular-level experiments confirmed the interaction between TME-related factors and the tumor microenvironment in HCC. To further validate the predictive power of the ICI score, a clinical cohort study was conducted at an independent clinical center. Results By evaluating immune gene expression levels, immune cell abundance, Immunescore, and Stromalscore, we initially identified three distinct immune subtypes of HCC, each showing significant differences in survival rates and heterogeneity. Subsequently, DEGs from 1022 immune subtypes were used to classify HCC samples into three immune genotypes, each characterized by distinct prognosis and tumor immune microenvironment (TIME) profiles. Furthermore, we developed the ICI score, a novel immunophenotyping method for HCC, which revealed significant variations based on gender, stage, progression, and DNA mutation profiles (p < 0.05). The ICI score also effectively predicted responses to immunotherapies, particularly through the chemokine signaling, focal adhesion, and JAK/STAT signaling pathways. Conclusion This research demonstrated that TME and immunophenotyping clusters can enhance prognostic accuracy for HCC patients. The independent prognostic indicators identified underscore the connection between tumor phenotype and the immune environment in HCC.

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免疫细胞稳态在肝细胞癌研究和治疗反应中的作用。
近年来,肿瘤微环境中的免疫细胞(TME)在调节癌症进展和治疗反应中变得至关重要。肿瘤和免疫细胞之间的动态相互作用正在成为一种很有前途的策略,可以激活宿主的免疫系统来对抗各种癌症。肝细胞癌(HCC)的发生和发展涉及复杂的生物学过程,TME和肿瘤表型的作用尚不完全清楚。因此,有必要研究免疫细胞稳态在HCC中的重要性。此外,了解肿瘤-免疫细胞相互作用的分子机制和生物学功能对于改善临床治疗效果越来越重要。方法从公共数据库和现实世界独立临床队列中选择790例HCC样本。将机器学习方法应用于这些样本,重点关注免疫相关指标。采用Boruta算法制定ICI评分,用于评估患者预后并预测对免疫治疗的反应。此外,还进行了一种新的肝癌免疫亚型分析。细胞水平实验证实了肝癌中tme相关因子与肿瘤微环境的相互作用。为了进一步验证ICI评分的预测能力,在一个独立的临床中心进行了一项临床队列研究。通过评估免疫基因表达水平、免疫细胞丰度、Immunescore和Stromalscore,我们初步确定了三种不同的HCC免疫亚型,每种亚型在生存率和异质性上都有显著差异。随后,使用来自1022种免疫亚型的deg将HCC样本分为三种免疫基因型,每种基因型都具有不同的预后和肿瘤免疫微环境(TIME)特征。此外,我们开发了ICI评分,这是一种新的HCC免疫分型方法,它揭示了基于性别、分期、进展和DNA突变谱的显著差异
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来源期刊
Clinical and Experimental Medicine
Clinical and Experimental Medicine 医学-医学:研究与实验
CiteScore
4.80
自引率
2.20%
发文量
159
审稿时长
2.5 months
期刊介绍: Clinical and Experimental Medicine (CEM) is a multidisciplinary journal that aims to be a forum of scientific excellence and information exchange in relation to the basic and clinical features of the following fields: hematology, onco-hematology, oncology, virology, immunology, and rheumatology. The journal publishes reviews and editorials, experimental and preclinical studies, translational research, prospectively designed clinical trials, and epidemiological studies. Papers containing new clinical or experimental data that are likely to contribute to changes in clinical practice or the way in which a disease is thought about will be given priority due to their immediate importance. Case reports will be accepted on an exceptional basis only, and their submission is discouraged. The major criteria for publication are clarity, scientific soundness, and advances in knowledge. In compliance with the overwhelmingly prevailing request by the international scientific community, and with respect for eco-compatibility issues, CEM is now published exclusively online.
期刊最新文献
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