Immunohistochemical Profiling of Immune Checkpoints in Chronic Hepatitis B Liver Tissue
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...
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MDPI AG
2025-06-01
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| Online Access: | https://www.mdpi.com/2076-0817/14/6/596 |
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| author | João Panão-Costa Rui Caetano Oliveira Paulo Teixeira Francisco Caramelo Maria Augusta Cipriano Olga Borges Armando Carvalho |
| author_facet | João Panão-Costa Rui Caetano Oliveira Paulo Teixeira Francisco Caramelo Maria Augusta Cipriano Olga Borges Armando Carvalho |
| author_sort | João Panão-Costa |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-2284e611e34a40deb397cbbf769df6a1 |
| institution | DOAJ |
| issn | 2076-0817 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pathogens |
| spelling | doaj-art-2284e611e34a40deb397cbbf769df6a12025-08-20T03:16:24ZengMDPI AGPathogens2076-08172025-06-0114659610.3390/pathogens14060596Immunohistochemical Profiling of Immune Checkpoints in Chronic Hepatitis B Liver TissueJoão Panão-Costa0Rui Caetano Oliveira1Paulo Teixeira2Francisco Caramelo3Maria Augusta Cipriano4Olga Borges5Armando Carvalho6CNC-UC—Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, PortugalDepartment of Pathology, Centro Hospitalar e Universitário de Coimbra, 3000-075 Coimbra, PortugalDepartment of Pathology, Centro Hospitalar e Universitário de Coimbra, 3000-075 Coimbra, PortugalCIBB—Center for Innovative Biomedicine and Biotechnology, University of Coimbra, 3004-504 Coimbra, PortugalDepartment of Pathology, Centro Hospitalar e Universitário de Coimbra, 3000-075 Coimbra, PortugalCNC-UC—Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, PortugalCentro Hospitalar e Universitário de Coimbra, 3004-561 Coimbra, PortugalChronic 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.https://www.mdpi.com/2076-0817/14/6/596chronic hepatitis Bimmune checkpoint receptorsimmune checkpoint inhibitorsimmune checkpoint blockadeimmune exhaustionimmunotherapy |
| spellingShingle | João Panão-Costa Rui Caetano Oliveira Paulo Teixeira Francisco Caramelo Maria Augusta Cipriano Olga Borges Armando Carvalho Immunohistochemical Profiling of Immune Checkpoints in Chronic Hepatitis B Liver Tissue Pathogens chronic hepatitis B immune checkpoint receptors immune checkpoint inhibitors immune checkpoint blockade immune exhaustion immunotherapy |
| title | Immunohistochemical Profiling of Immune Checkpoints in Chronic Hepatitis B Liver Tissue |
| title_full | Immunohistochemical Profiling of Immune Checkpoints in Chronic Hepatitis B Liver Tissue |
| title_fullStr | Immunohistochemical Profiling of Immune Checkpoints in Chronic Hepatitis B Liver Tissue |
| title_full_unstemmed | Immunohistochemical Profiling of Immune Checkpoints in Chronic Hepatitis B Liver Tissue |
| title_short | Immunohistochemical Profiling of Immune Checkpoints in Chronic Hepatitis B Liver Tissue |
| title_sort | immunohistochemical profiling of immune checkpoints in chronic hepatitis b liver tissue |
| topic | chronic hepatitis B immune checkpoint receptors immune checkpoint inhibitors immune checkpoint blockade immune exhaustion immunotherapy |
| url | https://www.mdpi.com/2076-0817/14/6/596 |
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