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

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

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article numbere32493
JournalPLoS One
Volume7
Issue number3
DOIs
Publication statusPublished - Mar 2 2012

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resection
hepatoma
Liver
Tumors
Hepatocellular Carcinoma
Recurrence
Messenger RNA
liver
Natural Killer T-Cells
T-cells
neoplasms
Survival
cells
Ligands
T-Lymphocytes
Data storage equipment
Neoplasms
T-lymphocytes
Tumor Microenvironment

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Cariani, E., Pilli, M., Zerbini, A., Rota, C., Olivani, A., Pelosi, G., ... Missale, G. (2012). Immunological and molecular correlates of disease recurrence after liver resection for hepatocellular carcinoma. PLoS One, 7(3), [e32493]. https://doi.org/10.1371/journal.pone.0032493

Immunological and molecular correlates of disease recurrence after liver resection for hepatocellular carcinoma. / Cariani, Elisabetta; Pilli, Massimo; Zerbini, Alessandro; Rota, Cristina; Olivani, Andrea; Pelosi, Guido; Schianchi, Claudia; Soliani, Paolo; Campanini, Nicoletta; Silini, Enrico Maria; Trenti, Tommaso; Ferrari, Carlo; Missale, Gabriele.

In: PLoS One, Vol. 7, No. 3, e32493, 02.03.2012.

Research output: Contribution to journalArticle

Cariani, E, Pilli, M, Zerbini, A, Rota, C, Olivani, A, Pelosi, G, Schianchi, C, Soliani, P, Campanini, N, Silini, EM, Trenti, T, Ferrari, C & Missale, G 2012, 'Immunological and molecular correlates of disease recurrence after liver resection for hepatocellular carcinoma', PLoS One, vol. 7, no. 3, e32493. https://doi.org/10.1371/journal.pone.0032493
Cariani, Elisabetta ; Pilli, Massimo ; Zerbini, Alessandro ; Rota, Cristina ; Olivani, Andrea ; Pelosi, Guido ; Schianchi, Claudia ; Soliani, Paolo ; Campanini, Nicoletta ; Silini, Enrico Maria ; Trenti, Tommaso ; Ferrari, Carlo ; Missale, Gabriele. / Immunological and molecular correlates of disease recurrence after liver resection for hepatocellular carcinoma. In: PLoS One. 2012 ; Vol. 7, No. 3.
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