High CD49a+ NK cell infiltrate is associated with poor clinical outcomes in Hepatocellular Carcinoma
NK cells infiltrating Hepatocellular Carcinoma (HCC) may express residency markers such as Integrin Subunit Alpha 1 (CD49a) that have been associated with nurturing functions in the decidua, and characterized by the production of angiogenic factors as well as loss of cytotoxicity. CIBERSORT, a compu...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2023-12-01
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| Series: | Heliyon |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844023098882 |
| _version_ | 1827577550129332224 |
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| author | Alessandra Zecca Valeria Barili Carolina Boni Paola Fisicaro Andrea Vecchi Marzia Rossi Valentina Reverberi Anna Montali Giuseppe Pedrazzi Carlo Ferrari Elisabetta Cariani Gabriele Missale |
| author_facet | Alessandra Zecca Valeria Barili Carolina Boni Paola Fisicaro Andrea Vecchi Marzia Rossi Valentina Reverberi Anna Montali Giuseppe Pedrazzi Carlo Ferrari Elisabetta Cariani Gabriele Missale |
| author_sort | Alessandra Zecca |
| collection | DOAJ |
| description | NK cells infiltrating Hepatocellular Carcinoma (HCC) may express residency markers such as Integrin Subunit Alpha 1 (CD49a) that have been associated with nurturing functions in the decidua, and characterized by the production of angiogenic factors as well as loss of cytotoxicity. CIBERSORT, a computational analysis method for quantifying cell fractions from bulk tissue gene expression profiles, was used to estimate the infiltrating immune cell composition of the tumor microenvironment from gene expression profiles of a large cohort of 225 HCCs in the public GEO database. Decidual-like CD49a+ NK cells, in addition to another 22 immune cell populations, were characterized and thoroughly investigated so that HCC cell heterogeneity in a large cohort of 225 HCCs from the public GEO database could be studied. An inverse correlation of the expression of CD49a+ NK-cells and CD8+ T-cells suggested a negative association with clinical outcomes. This result was confirmed in a further validation cohort of 100 HCC patients from The Cancer Genome Atlas, Liver Hepatocellular Carcinoma (TCGA-LIHC). Cox regression analysis did not identify CD49a+ cells as a variable independently associated with survival. However, a more abundant infiltrate of this subset was present in patients at a more advanced pathological and clinical HCC stage. In conclusion, we found that NK cells, with a decidual-like gene expression profile, are enriched in HCC, and their abundance increases not only in tumor size but also at advanced stages of the disease suggesting that these cells play a role in tumor growth. For this reason, these NK cells may represent a possible new target for immunotherapeutic approaches in HCC. |
| first_indexed | 2024-03-08T21:28:24Z |
| format | Article |
| id | doaj.art-9cb91cef7d1848ba8120be1bd442b707 |
| institution | Directory Open Access Journal |
| issn | 2405-8440 |
| language | English |
| last_indexed | 2024-03-08T21:28:24Z |
| publishDate | 2023-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj.art-9cb91cef7d1848ba8120be1bd442b7072023-12-21T07:34:16ZengElsevierHeliyon2405-84402023-12-01912e22680High CD49a+ NK cell infiltrate is associated with poor clinical outcomes in Hepatocellular CarcinomaAlessandra Zecca0Valeria Barili1Carolina Boni2Paola Fisicaro3Andrea Vecchi4Marzia Rossi5Valentina Reverberi6Anna Montali7Giuseppe Pedrazzi8Carlo Ferrari9Elisabetta Cariani10Gabriele Missale11Unit of Infectious Diseases and Hepatology, Laboratory of Viral Immunopathology, Azienda Ospedaliero–Universitaria of Parma, 43126 Parma, ItalyDepartment of Medicine and Surgery, University of Parma, 43126 Parma, ItalyUnit of Infectious Diseases and Hepatology, Laboratory of Viral Immunopathology, Azienda Ospedaliero–Universitaria of Parma, 43126 Parma, ItalyUnit of Infectious Diseases and Hepatology, Laboratory of Viral Immunopathology, Azienda Ospedaliero–Universitaria of Parma, 43126 Parma, ItalyUnit of Infectious Diseases and Hepatology, Laboratory of Viral Immunopathology, Azienda Ospedaliero–Universitaria of Parma, 43126 Parma, ItalyDepartment of Medicine and Surgery, University of Parma, 43126 Parma, ItalyUnit of Infectious Diseases and Hepatology, Laboratory of Viral Immunopathology, Azienda Ospedaliero–Universitaria of Parma, 43126 Parma, ItalyDepartment of Medicine and Surgery, University of Parma, 43126 Parma, ItalyDepartment of Medicine and Surgery, University of Parma, 43126 Parma, ItalyUnit of Infectious Diseases and Hepatology, Laboratory of Viral Immunopathology, Azienda Ospedaliero–Universitaria of Parma, 43126 Parma, Italy; Department of Medicine and Surgery, University of Parma, 43126 Parma, ItalyIndependent Researcher, ItalyUnit of Infectious Diseases and Hepatology, Laboratory of Viral Immunopathology, Azienda Ospedaliero–Universitaria of Parma, 43126 Parma, Italy; Department of Medicine and Surgery, University of Parma, 43126 Parma, Italy; Corresponding author. Unit of Infectious Diseases and Hepatology, Laboratory of Viral Immunopathology, Azienda Ospedaliero–Universitaria of Parma, 43126 Parma, Italy.NK cells infiltrating Hepatocellular Carcinoma (HCC) may express residency markers such as Integrin Subunit Alpha 1 (CD49a) that have been associated with nurturing functions in the decidua, and characterized by the production of angiogenic factors as well as loss of cytotoxicity. CIBERSORT, a computational analysis method for quantifying cell fractions from bulk tissue gene expression profiles, was used to estimate the infiltrating immune cell composition of the tumor microenvironment from gene expression profiles of a large cohort of 225 HCCs in the public GEO database. Decidual-like CD49a+ NK cells, in addition to another 22 immune cell populations, were characterized and thoroughly investigated so that HCC cell heterogeneity in a large cohort of 225 HCCs from the public GEO database could be studied. An inverse correlation of the expression of CD49a+ NK-cells and CD8+ T-cells suggested a negative association with clinical outcomes. This result was confirmed in a further validation cohort of 100 HCC patients from The Cancer Genome Atlas, Liver Hepatocellular Carcinoma (TCGA-LIHC). Cox regression analysis did not identify CD49a+ cells as a variable independently associated with survival. However, a more abundant infiltrate of this subset was present in patients at a more advanced pathological and clinical HCC stage. In conclusion, we found that NK cells, with a decidual-like gene expression profile, are enriched in HCC, and their abundance increases not only in tumor size but also at advanced stages of the disease suggesting that these cells play a role in tumor growth. For this reason, these NK cells may represent a possible new target for immunotherapeutic approaches in HCC.http://www.sciencedirect.com/science/article/pii/S2405844023098882 |
| spellingShingle | Alessandra Zecca Valeria Barili Carolina Boni Paola Fisicaro Andrea Vecchi Marzia Rossi Valentina Reverberi Anna Montali Giuseppe Pedrazzi Carlo Ferrari Elisabetta Cariani Gabriele Missale High CD49a+ NK cell infiltrate is associated with poor clinical outcomes in Hepatocellular Carcinoma Heliyon |
| title | High CD49a+ NK cell infiltrate is associated with poor clinical outcomes in Hepatocellular Carcinoma |
| title_full | High CD49a+ NK cell infiltrate is associated with poor clinical outcomes in Hepatocellular Carcinoma |
| title_fullStr | High CD49a+ NK cell infiltrate is associated with poor clinical outcomes in Hepatocellular Carcinoma |
| title_full_unstemmed | High CD49a+ NK cell infiltrate is associated with poor clinical outcomes in Hepatocellular Carcinoma |
| title_short | High CD49a+ NK cell infiltrate is associated with poor clinical outcomes in Hepatocellular Carcinoma |
| title_sort | high cd49a nk cell infiltrate is associated with poor clinical outcomes in hepatocellular carcinoma |
| url | http://www.sciencedirect.com/science/article/pii/S2405844023098882 |
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