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Theses

Phenotypic and Functional Evaluation of the Intra-hepatic Populations of Lymphocytes during Hepatocellular carcinoma

Abstract : Immune cells infiltrating the liver (CD3 +, CD4 +, CD8 +, CD20 +, CD56 +, TCRγδ +, FoxP3 + and CD123 +) are more likely (p <0.05) in areas with cirrhosis compared to areas tumor in 2 cases of hepatocellular carcinoma (induced by Hepatitis C (HCV-HCC) or alcohol (HCC-OH)). The expression levels of tumor in the group CD8β HCV and HCC-CD8α and IFN-γ in the HCC-OH group are higher (p <0.05) than those areas with cirrhosis. Comparisons of cirrhosis cancer show that CD3 +, CD4 +, CD8 +, CD20 +, FoxP3 +, CD123 + and TCRγδ + (p = 0,089) and the ratios CD3/CD20, FoxP3/CD4 are higher (p <0.05) in cirrhosis HCV than in OH. The expression levels of IFN-γ, CD8α and perforin were lower (p <0.05) in cirrhosis in HCV cirrhosis OH. In addition, the number of CD8 + cells correlates with that of FoxP3 + cells in the parenchymal nodules in cirrhosis whereas HCV is the level of expression of IFN-γ and perforin for cirrhosis OH . The results for the HCC-HCV and cirrhosis C without cancer show that CD3 +, CD4 +, CD20 + and CD8 + cells are more numerous in cirrhosis cancer (p <0.05) but the number of CD56 + (p = 0.067) and CD3/CD20 ratio (P <0.05) was lower in cirrhosis cancer. TGF-β and IFN-γ are correlated in cirrhosis C. No differences were observed within the tumors in the 2 groups at the cellular and transcriptional level with the exception of CD8α, lower in HCV-HCC group (p <0.05). The number of intratumoral FoxP3 + cells is positively correlated with that of CD4 and CD8 + cells and negatively with tumor expression of perforin. In tumors, positive correlations between the number of CD4 + and CD8 +, CD56 + and TCRγδ +, perforin with IFN-γ and RANTES were also observed. It is important to note that the CD3 + cells are almost always correlated with CD20 + in all areas and groups. Regarding the immunity-related tumor aggressiveness, the levels of ALT, AFP and METAVIR score were correlated with CD3 +, CD4 + TCRγδ + and in HCV-HCC group. Tumor size is correlated with age in the two groups and with the expression of FoxP3 in the HCC-HCV group. Tumor necrosis is greater (p <0.05) in the HCC-OH and inversely correlated with age and the expression of RANTES in the 2 groups. The Ki67 labeling is positively correlated with ALT, AFP, PT and viremia and inversely with the level of intra-tumoral perforin. In the 2 groups, the number of FoxP3 + cells is inversely correlated with the bilirubin. Relapse is more frequent (p <0.05) in the HCV-HCC. For patients who relapse, the number of CD3 +, CD4 +, CD8 +, CD20 + and FoxP3 + is higher (p <0.05) in areas with cirrhosis, while the number of cells CD123 + and the ratio FoxP3 + / CD4 + were higher (p <0.05 ) in the tumor. In addition, a significant reduction in the frequency of NK cells and report CD56bright/dim is observed for hepatitis C compared to B. The proportion of intrahepatic NK cell CD158a, CD158b and h +, j + is lower than in the peripheral blood in patients with HCV + and in the liver of HBV + patients. The frequency of NKG2A + NK is lower in the blood and liver of HBV + patients compared with HCV +. For patients with HCV +, i) CD56 + intrahepatic localize preferentially out of necrosis when the necroinflammatory activity increases and ii) cells circulating CD3-CD56brightNKG2A + correlated positively with the extension of necro-inflammation and fibrosis. In addition, in patients chronically HCV +, FoxP3 + cells located in areas necroinflammatory are predominantly associated with CD8 + T cells and positively correlated with CD8 + cells and the METAVIR fibrosis score. Overall, many tumor-infiltrating cells appear to be less active and associated with relapse and poor prognosis. NK cells and regulatory in chronic hepatitis C could be of great interest in monitoring the disease.
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https://tel.archives-ouvertes.fr/tel-00620416
Contributor : Ramzan Muhammad <>
Submitted on : Thursday, September 8, 2011 - 10:05:42 AM
Last modification on : Friday, November 6, 2020 - 4:04:01 AM
Long-term archiving on: : Friday, December 9, 2011 - 2:21:03 AM

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  • HAL Id : tel-00620416, version 1

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U823 | UJF | UGA

Citation

Ramzan Muhammad. Phenotypic and Functional Evaluation of the Intra-hepatic Populations of Lymphocytes during Hepatocellular carcinoma. Immunology. Université Joseph-Fourier - Grenoble I, 2009. English. ⟨tel-00620416⟩

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