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慢性乙型肝炎肝组织中免疫检查点的免疫组织化学分析

Immunohistochemical Profiling of Immune Checkpoints in Chronic Hepatitis B Liver Tissue.

作者信息

Panão-Costa João, Oliveira Rui Caetano, Teixeira Paulo, Caramelo Francisco, Cipriano Maria Augusta, Borges Olga, Carvalho Armando

机构信息

CNC-UC-Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal.

CIBB-Center for Innovative Biomedicine and Biotechnology, University of Coimbra, 3004-504 Coimbra, Portugal.

出版信息

Pathogens. 2025 Jun 18;14(6):596. doi: 10.3390/pathogens14060596.

Abstract

Chronic hepatitis B (CHB) remains a significant global health concern due to complications like cirrhosis and liver cancer. Immune cell exhaustion, characterized by increased suppressive molecules and inhibitory receptors, represents a critical feature of CHB. Understanding the mechanisms of hepatic immune exhaustion in CHB patients is imperative for the development of effective therapeutic interventions. In this study, we investigated the expression levels and histological distribution of various immune checkpoint receptors and ligands in liver biopsies obtained from CHB patients. Additionally, we aimed to evaluate potential concurrent overexpression of specific receptors and their association with clinical parameters such as ALT levels. Our analysis revealed that PD-1, PD-L1, CTLA-4, TIM-3, GAL-9, CD272, TIGIT, and 2B4 exhibited predominant localization in portal tracts and sinusoids. Furthermore, we observed a correlation between the expression of PD-1, TIM-3, and GAL-9 with ALT levels in CHB patients. Additionally, a strong relationship was identified between the expression of CD272 and TIGIT, as well as between GAL-9 and CTLA-4 within the studied population. Our findings underscore the significance of the TIM-3:GAL-9 pathway in the immunopathogenesis of CHB. This detailed analysis sets the stage for future combined immunotherapy strategies aimed at leveraging checkpoint receptors to enhance clinical outcomes.

摘要

慢性乙型肝炎(CHB)由于诸如肝硬化和肝癌等并发症,仍然是全球重大的健康问题。以抑制分子和抑制性受体增加为特征的免疫细胞耗竭是CHB的一个关键特征。了解CHB患者肝脏免疫耗竭的机制对于开发有效的治疗干预措施至关重要。在本研究中,我们调查了从CHB患者获得的肝活检组织中各种免疫检查点受体和配体的表达水平及组织学分布。此外,我们旨在评估特定受体潜在的同时过度表达及其与诸如ALT水平等临床参数的关联。我们的分析显示,PD-1、PD-L1、CTLA-4、TIM-3、GAL-9、CD272、TIGIT和2B4在门管区和肝血窦中呈现主要定位。此外,我们观察到CHB患者中PD-1、TIM-3和GAL-9的表达与ALT水平之间存在相关性。另外,在所研究人群中,还确定了CD272与TIGIT的表达之间以及GAL-9与CTLA-4的表达之间存在密切关系。我们的研究结果强调了TIM-3:GAL-9通路在CHB免疫发病机制中的重要性。这一详细分析为未来旨在利用检查点受体以改善临床结局的联合免疫治疗策略奠定了基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3960/12196340/176eb8f1e6de/pathogens-14-00596-g001.jpg

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