Immunological and molecular correlates of disease recurrence after liver resection for hepatocellular carcinoma.

The definition of the risk of hepatocellular carcinoma (HCC) recurrence after resection represents a central issue to improve the clinical management of patients. In this study we examined the prognostic relevance of infiltrating immune cell subsets in the tumor (TIL) and in nontumorous (NT) liver (...

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Autores principales: Elisabetta Cariani, Massimo Pilli, Alessandro Zerbini, Cristina Rota, Andrea Olivani, Guido Pelosi, Claudia Schianchi, Paolo Soliani, Nicoletta Campanini, Enrico Maria Silini, Tommaso Trenti, Carlo Ferrari, Gabriele Missale
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Publicado: Public Library of Science (PLoS) 2012
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Acceso en línea:https://doaj.org/article/ce40c29676b6456492e107d17b9532b0
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spelling oai:doaj.org-article:ce40c29676b6456492e107d17b9532b02021-11-18T07:26:14ZImmunological and molecular correlates of disease recurrence after liver resection for hepatocellular carcinoma.1932-620310.1371/journal.pone.0032493https://doaj.org/article/ce40c29676b6456492e107d17b9532b02012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22396772/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203The definition of the risk of hepatocellular carcinoma (HCC) recurrence after resection represents a central issue to improve the clinical management of patients. In this study we examined the prognostic relevance of infiltrating immune cell subsets in the tumor (TIL) and in nontumorous (NT) liver (LIL), and the expression of immune-related and lineage-specific mRNAs in HCC and NT liver derived from 42 patients. The phenotype of infiltrating cells was analyzed by flow cytometry, and mRNA expression in liver tissue was examined by real-time reverse transcription (RT)-PCR. The tumor immune microenvironment was enriched in inhibitory and dysfunctional cell subsets. Enrichment in CD4+ T-cells and in particular CD4 and CD8+ memory subsets within TIL was predictive of better overall survival (OS) and time to recurrence (TTR). Increased programmed death ligand 1 (PDL1) mRNA content and higher prevalence of invariant NKT (iNKT) cells were associated with shorter OS and TTR, respectively. By combined evaluation of infiltrating cell subsets along with mRNA profiling of immune and tumor related genes, we identified the intratumoral frequency of memory T-cells and iNKT-cells as well as PDL1 expression as the best predictors of clinical outcome. HCC infiltrate is characterized by the expression of molecules with negative regulatory function that may favor tumor recurrence and poor survival.Elisabetta CarianiMassimo PilliAlessandro ZerbiniCristina RotaAndrea OlivaniGuido PelosiClaudia SchianchiPaolo SolianiNicoletta CampaniniEnrico Maria SiliniTommaso TrentiCarlo FerrariCarlo FerrariGabriele MissalePublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 3, p e32493 (2012)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Elisabetta Cariani
Massimo Pilli
Alessandro Zerbini
Cristina Rota
Andrea Olivani
Guido Pelosi
Claudia Schianchi
Paolo Soliani
Nicoletta Campanini
Enrico Maria Silini
Tommaso Trenti
Carlo Ferrari
Carlo Ferrari
Gabriele Missale
Immunological and molecular correlates of disease recurrence after liver resection for hepatocellular carcinoma.
description The definition of the risk of hepatocellular carcinoma (HCC) recurrence after resection represents a central issue to improve the clinical management of patients. In this study we examined the prognostic relevance of infiltrating immune cell subsets in the tumor (TIL) and in nontumorous (NT) liver (LIL), and the expression of immune-related and lineage-specific mRNAs in HCC and NT liver derived from 42 patients. The phenotype of infiltrating cells was analyzed by flow cytometry, and mRNA expression in liver tissue was examined by real-time reverse transcription (RT)-PCR. The tumor immune microenvironment was enriched in inhibitory and dysfunctional cell subsets. Enrichment in CD4+ T-cells and in particular CD4 and CD8+ memory subsets within TIL was predictive of better overall survival (OS) and time to recurrence (TTR). Increased programmed death ligand 1 (PDL1) mRNA content and higher prevalence of invariant NKT (iNKT) cells were associated with shorter OS and TTR, respectively. By combined evaluation of infiltrating cell subsets along with mRNA profiling of immune and tumor related genes, we identified the intratumoral frequency of memory T-cells and iNKT-cells as well as PDL1 expression as the best predictors of clinical outcome. HCC infiltrate is characterized by the expression of molecules with negative regulatory function that may favor tumor recurrence and poor survival.
format article
author Elisabetta Cariani
Massimo Pilli
Alessandro Zerbini
Cristina Rota
Andrea Olivani
Guido Pelosi
Claudia Schianchi
Paolo Soliani
Nicoletta Campanini
Enrico Maria Silini
Tommaso Trenti
Carlo Ferrari
Carlo Ferrari
Gabriele Missale
author_facet Elisabetta Cariani
Massimo Pilli
Alessandro Zerbini
Cristina Rota
Andrea Olivani
Guido Pelosi
Claudia Schianchi
Paolo Soliani
Nicoletta Campanini
Enrico Maria Silini
Tommaso Trenti
Carlo Ferrari
Carlo Ferrari
Gabriele Missale
author_sort Elisabetta Cariani
title Immunological and molecular correlates of disease recurrence after liver resection for hepatocellular carcinoma.
title_short Immunological and molecular correlates of disease recurrence after liver resection for hepatocellular carcinoma.
title_full Immunological and molecular correlates of disease recurrence after liver resection for hepatocellular carcinoma.
title_fullStr Immunological and molecular correlates of disease recurrence after liver resection for hepatocellular carcinoma.
title_full_unstemmed Immunological and molecular correlates of disease recurrence after liver resection for hepatocellular carcinoma.
title_sort immunological and molecular correlates of disease recurrence after liver resection for hepatocellular carcinoma.
publisher Public Library of Science (PLoS)
publishDate 2012
url https://doaj.org/article/ce40c29676b6456492e107d17b9532b0
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