title: Immunological and molecular correlates of disease recurrence after liver resection for hepatocellular carcinoma.
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.
authors.affiliation: Clinical Pathology-Toxicology, Ospedale S. Agostino-Estense, Modena, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Cariani
authors.forename: Massimo
authors.initials: M
authors.lastname: Pilli
authors.forename: Alessandro
authors.initials: A
authors.lastname: Zerbini
authors.forename: Cristina
authors.initials: C
authors.lastname: Rota
authors.forename: Andrea
authors.initials: A
authors.lastname: Olivani
authors.forename: Guido
authors.initials: G
authors.lastname: Pelosi
authors.forename: Claudia
authors.initials: C
authors.lastname: Schianchi
authors.forename: Paolo
authors.initials: P
authors.lastname: Soliani
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Campanini
authors.forename: Enrico Maria
authors.initials: EM
authors.lastname: Silini
authors.forename: Tommaso
authors.initials: T
authors.lastname: Trenti
authors.forename: Carlo
authors.initials: C
authors.lastname: Ferrari
authors.forename: Gabriele
authors.initials: G
authors.lastname: Missale
mesh_terms: D000368:Aged; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology; D006528:Carcinoma, Hepatocellular / Q000276:immunology* / Q000601:surgery*; D019070:Cell Lineage; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D007107:Immune System; D007150:Immunohistochemistry / Q000379:methods; D008099:Liver / Q000378:metabolism; D008113:Liver Neoplasms / Q000276:immunology* / Q000601:surgery*; D016246:Lymphocytes, Tumor-Infiltrating / Q000166:cytology; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism; D012008:Recurrence; D016896:Treatment Outcome
chemical_list: D012333:RNA, Messenger