Muhammad Ramzan1,2, Nathalie Sturm1,2,3, Thomas Decaens1,2,4, Paulette Bioulac-Sage5, Brigitte Bancel6,7,8, Philippe Merle7,8,9, Jeanne Tran Van Nhieu10, Rémy Slama1,2, Christian Letoublon1,2,11, Jean-Pierre Zarski1,2,4, Evelyne Jouvin-Marche1,2, Patrice N Marche1,2,4, Vincent Leroy1,2,4. 1. INSERM, Unité 823, Grenoble, France. 2. Université Grenoble-Alpes, Faculté de Médecine, UMR-S823, Grenoble, France. 3. Département d'Anatomie et de Cytologie Pathologiques, CHU de Grenoble, Grenoble, France. 4. Clinique d' Hépatogastroentérologie, pôle DigiDune, CHU de Grenoble, Grenoble, France. 5. Service d'Anatomie et de Cytologie Pathologiques, Hôpital Pellegrin, Bordeaux, France. 6. Service de Pathologie, Hôpital de la Croix Rousse, Lyon, France. 7. Université Claude Bernard Lyon 1, INSERM UMR-S1052, Centre de Recherche en Cancérologie de Lyon, Lyon, France. 8. Hospices Civils de Lyon, Lyon, France. 9. Service d'Hépatologie, Hôpital de la Croix-Rousse, Lyon, France. 10. Département de Pathologie, APHP, Groupe Hospitalier Henri Mondor, Val de Marne, Université Paris Est-Créteil, Créteil, France. 11. Clinique de Chirurgie Digestive, pôle DIGIDUNE, CHU de Grenoble, Grenoble, France.
Abstract
BACKGROUND: Chronic liver inflammation and immune/inflammatory response promote hepatocellular carcinoma. The aim of this study was to characterize the immune status of HCV-related cirrhosis in patients with hepatocellular carcinoma (HCV-HCC) as compared to HCV patients without hepatocellular carcinoma. METHOD: Immune markers (CD3, CD4, CD8, CD20, CD56, TCRγδ, FoxP3) and gene expression profiles (CD8α, CD8β, FoxP3, IL-6, IFN-γ, perforin, RANTES) were analysed in a test cohort by immunohistochemistry and quantitative RT-PCR analysis on serial non-tumorous and tumorous tissues. RESULTS: Immune micro-environment was more inflammatory in HCV-HCC than HCV cirrhotic livers. The number of CD3(+) , CD4(+) , CD8(+) and CD20(+) liver-infiltrating lymphocytes was significantly higher, whereas the number of CD56(+) cells was significantly lower in HCV-HCC compared to HCV cirrhotic parenchyma. These differences were restricted to fibrous septa for CD4(+) and CD20(+) cells and to nodular parenchyma for CD8(+) cells. Gene expressions of CD8α, FoxP3 and RANTES were also significantly higher in HCV-HCC than in HCV cirrhosis. Interestingly, in a large cohort of 63 HCV-HCC patients. The number of CD8(+) cells ≥100/field was associated with significant higher tumour recurrence (P = 0.003) and lower overall survival (P = 0.05) at 5 years. CONCLUSION: High densities of liver-infiltrating lymphocytes in HCV-HCC cirrhotic parenchyma prevail inflammatory conditions and could contribute to tumorigenesis and tumour recurrence. These results could contribute towards better clinical evaluation of patients susceptible for HCC recurrence after curative surgery.
BACKGROUND:Chronic liver inflammation and immune/inflammatory response promote hepatocellular carcinoma. The aim of this study was to characterize the immune status of HCV-related cirrhosis in patients with hepatocellular carcinoma (HCV-HCC) as compared to HCV patients without hepatocellular carcinoma. METHOD: Immune markers (CD3, CD4, CD8, CD20, CD56, TCRγδ, FoxP3) and gene expression profiles (CD8α, CD8β, FoxP3, IL-6, IFN-γ, perforin, RANTES) were analysed in a test cohort by immunohistochemistry and quantitative RT-PCR analysis on serial non-tumorous and tumorous tissues. RESULTS: Immune micro-environment was more inflammatory in HCV-HCC than HCV cirrhotic livers. The number of CD3(+) , CD4(+) , CD8(+) and CD20(+) liver-infiltrating lymphocytes was significantly higher, whereas the number of CD56(+) cells was significantly lower in HCV-HCC compared to HCV cirrhotic parenchyma. These differences were restricted to fibrous septa for CD4(+) and CD20(+) cells and to nodular parenchyma for CD8(+) cells. Gene expressions of CD8α, FoxP3 and RANTES were also significantly higher in HCV-HCC than in HCV cirrhosis. Interestingly, in a large cohort of 63 HCV-HCC patients. The number of CD8(+) cells ≥100/field was associated with significant higher tumour recurrence (P = 0.003) and lower overall survival (P = 0.05) at 5 years. CONCLUSION: High densities of liver-infiltrating lymphocytes in HCV-HCC cirrhotic parenchyma prevail inflammatory conditions and could contribute to tumorigenesis and tumour recurrence. These results could contribute towards better clinical evaluation of patients susceptible for HCC recurrence after curative surgery.
Authors: Sam Sheppard; Joana Guedes; Anna Mroz; Anastasia-Maria Zavitsanou; Hiromi Kudo; Stephen M Rothery; Panagiotis Angelopoulos; Robert Goldin; Nadia Guerra Journal: Nat Commun Date: 2017-01-27 Impact factor: 14.919
Authors: Wei Ding; Xuezhong Xu; Yan Qian; Wenbo Xue; Yibo Wang; Jianguo Du; Lei Jin; Yulin Tan Journal: Medicine (Baltimore) Date: 2018-12 Impact factor: 1.817