Decreased granzyme-B expression in CD11c+CD8+ T cells associated with disease progression in patients with HBV-related hepatocellular carcinoma
IntroductionCD11c+CD8+ T cells are an unconventional CD8+ T cell subset that exerts antiviral activity in infectious diseases. However, its characteristics in hepatocellular carcinoma (HCC) have not been elucidated.MethodsTwenty-six patients with hepatitis B virus (HBV)-related HCC and 25 healthy co...
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Frontiers Media S.A.
2023-01-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1107483/full |
| _version_ | 1797938740169015296 |
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| author | Lin Gao Lin Gao Zhixian Hong Guanglin Lei An-Liang Guo An-Liang Guo Fu-Sheng Wang Yan-Mei Jiao Junliang Fu |
| author_facet | Lin Gao Lin Gao Zhixian Hong Guanglin Lei An-Liang Guo An-Liang Guo Fu-Sheng Wang Yan-Mei Jiao Junliang Fu |
| author_sort | Lin Gao |
| collection | DOAJ |
| description | IntroductionCD11c+CD8+ T cells are an unconventional CD8+ T cell subset that exerts antiviral activity in infectious diseases. However, its characteristics in hepatocellular carcinoma (HCC) have not been elucidated.MethodsTwenty-six patients with hepatitis B virus (HBV)-related HCC and 25 healthy controls (HC) were enrolled. The frequency and phenotype of CD11c+CD8+ T cells in peripheral blood and tumors in situ were detected by flow cytometry and immunohistochemistry.ResultsBoth the HCC group and HC group had similar frequency and phenotype characteristics of CD11c+CD8+ T cells in the periphery. CD11c+CD8+ T cells were mainly composed of effector T cells, most of which were CD45RA+CCR7-. Compared with CD11c-CD8+ T cells, CD11c+CD8+ T cells had a higher proportion of CD38 and HLA-DR double positive, and expressed high levels of granzyme-B (GB) and degranulation marker CD107a, and produced high levels of interleukin-2 (IL-2), tumor necrosis factor alpha (TNF-α) and interferon-gamma (IFN-γ). However, the ability of degranulation and TNF-α production of CD11c+CD8+ T cells in patients with HCC were significantly lower than that in healthy controls. The GB expression level of peripheral CD11c+CD8+ T cells in patients with advanced stage of HCC was significantly lower than that in patients with early stage of HCC, and the GB expression level of liver-infiltrating CD11c+CD8+ T cells in tumor tissues was lower than that in non-tumor tissues. More importantly, the GB expression level of peripheral CD11c+CD8+ T cells was negatively correlated with tumor volume. ConclusionsThese findings indicate that CD11c+CD8+ T cells may have potential anti-tumor activity and that GB+CD11c+CD8+ T cells are associated with disease progression in patients with HBV-related HCC. |
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| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-10T19:04:26Z |
| publishDate | 2023-01-01 |
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| spelling | doaj.art-53eef6d8c6494f41a8395bd127919ceb2023-01-31T04:55:56ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-01-011410.3389/fimmu.2023.11074831107483Decreased granzyme-B expression in CD11c+CD8+ T cells associated with disease progression in patients with HBV-related hepatocellular carcinomaLin Gao0Lin Gao1Zhixian Hong2Guanglin Lei3An-Liang Guo4An-Liang Guo5Fu-Sheng Wang6Yan-Mei Jiao7Junliang Fu8Senior Department of Infectious Diseases, The Fifth Medical Center of Chinese People's Liberation Army (PLA) General Hospital, National Clinical Research Center for Infectious Diseases, Beijing, ChinaDepartment of Infectious Disease and Hepatology, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, ChinaSenior Department of Hepatology, The Fifth Medical Center of Chinese People's Liberation Army (PLA) General Hospital, Beijing, ChinaSenior Department of Hepatology, The Fifth Medical Center of Chinese People's Liberation Army (PLA) General Hospital, Beijing, ChinaSenior Department of Infectious Diseases, The Fifth Medical Center of Chinese People's Liberation Army (PLA) General Hospital, National Clinical Research Center for Infectious Diseases, Beijing, ChinaCenter for Reproductive Medicine, Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Jinan, ChinaSenior Department of Infectious Diseases, The Fifth Medical Center of Chinese People's Liberation Army (PLA) General Hospital, National Clinical Research Center for Infectious Diseases, Beijing, ChinaSenior Department of Infectious Diseases, The Fifth Medical Center of Chinese People's Liberation Army (PLA) General Hospital, National Clinical Research Center for Infectious Diseases, Beijing, ChinaSenior Department of Infectious Diseases, The Fifth Medical Center of Chinese People's Liberation Army (PLA) General Hospital, National Clinical Research Center for Infectious Diseases, Beijing, ChinaIntroductionCD11c+CD8+ T cells are an unconventional CD8+ T cell subset that exerts antiviral activity in infectious diseases. However, its characteristics in hepatocellular carcinoma (HCC) have not been elucidated.MethodsTwenty-six patients with hepatitis B virus (HBV)-related HCC and 25 healthy controls (HC) were enrolled. The frequency and phenotype of CD11c+CD8+ T cells in peripheral blood and tumors in situ were detected by flow cytometry and immunohistochemistry.ResultsBoth the HCC group and HC group had similar frequency and phenotype characteristics of CD11c+CD8+ T cells in the periphery. CD11c+CD8+ T cells were mainly composed of effector T cells, most of which were CD45RA+CCR7-. Compared with CD11c-CD8+ T cells, CD11c+CD8+ T cells had a higher proportion of CD38 and HLA-DR double positive, and expressed high levels of granzyme-B (GB) and degranulation marker CD107a, and produced high levels of interleukin-2 (IL-2), tumor necrosis factor alpha (TNF-α) and interferon-gamma (IFN-γ). However, the ability of degranulation and TNF-α production of CD11c+CD8+ T cells in patients with HCC were significantly lower than that in healthy controls. The GB expression level of peripheral CD11c+CD8+ T cells in patients with advanced stage of HCC was significantly lower than that in patients with early stage of HCC, and the GB expression level of liver-infiltrating CD11c+CD8+ T cells in tumor tissues was lower than that in non-tumor tissues. More importantly, the GB expression level of peripheral CD11c+CD8+ T cells was negatively correlated with tumor volume. ConclusionsThese findings indicate that CD11c+CD8+ T cells may have potential anti-tumor activity and that GB+CD11c+CD8+ T cells are associated with disease progression in patients with HBV-related HCC.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1107483/fullCD11cCD8 T cellshepatocellular carcinomahepatitis B virusanti-tumor |
| spellingShingle | Lin Gao Lin Gao Zhixian Hong Guanglin Lei An-Liang Guo An-Liang Guo Fu-Sheng Wang Yan-Mei Jiao Junliang Fu Decreased granzyme-B expression in CD11c+CD8+ T cells associated with disease progression in patients with HBV-related hepatocellular carcinoma Frontiers in Immunology CD11c CD8 T cells hepatocellular carcinoma hepatitis B virus anti-tumor |
| title | Decreased granzyme-B expression in CD11c+CD8+ T cells associated with disease progression in patients with HBV-related hepatocellular carcinoma |
| title_full | Decreased granzyme-B expression in CD11c+CD8+ T cells associated with disease progression in patients with HBV-related hepatocellular carcinoma |
| title_fullStr | Decreased granzyme-B expression in CD11c+CD8+ T cells associated with disease progression in patients with HBV-related hepatocellular carcinoma |
| title_full_unstemmed | Decreased granzyme-B expression in CD11c+CD8+ T cells associated with disease progression in patients with HBV-related hepatocellular carcinoma |
| title_short | Decreased granzyme-B expression in CD11c+CD8+ T cells associated with disease progression in patients with HBV-related hepatocellular carcinoma |
| title_sort | decreased granzyme b expression in cd11c cd8 t cells associated with disease progression in patients with hbv related hepatocellular carcinoma |
| topic | CD11c CD8 T cells hepatocellular carcinoma hepatitis B virus anti-tumor |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1107483/full |
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