Thématique :
- Foie
Originalité :
Solidité :
Doit faire évoluer notre pratique :
Pas encore
Nom du veilleur :
Professeur Jean-Marie PERON
Coup de coeur :
  2017 Sep;153(3):812-826.  
  doi: 10.1053/j.gastro.2017.06.007.  
  Identification of an Immune-specific Class of Hepatocellular Carcinoma, Based on Molecular Features  
  Sia D, Jiao Y, Martinez-Quetglas I, Kuchuk O, Villacorta-Martin C, Castro de Moura M, Putra J, Camprecios G, Bassaganyas L, Akers N, Losic B, Waxman S, Thung SN, Mazzaferro V, Esteller M, Friedman SL, Schwartz M, Villanueva A, Llovet JM  



Agents that induce an immune response against tumors by altering T-cell regulation have increased survival times of patients with advanced-stage tumors, such as melanoma or lung cancer. We aimed to characterize molecular features of immune cells that infiltrate hepatocellular carcinomas (HCCs) to determine whether these types of agents might be effective against liver tumors.


We analyzed HCC samples from 956 patients. We separated gene expression profiles from tumor, stromal, and immune cells using a non-negative matrix factorization algorithm. We then analyzed the gene expression pattern of inflammatory cells in HCC tumor samples. We correlated expression patterns with the presence of immune cell infiltrates and immune regulatory molecules, determined by pathology and immunohistochemical analyses, in a training set of 228 HCC samples. We validated the correlation in a validation set of 728 tumor samples. Using data from 190 tumors in the Cancer Genome Atlas, we correlated immune cell gene expression profiles with numbers of chromosomal aberrations (based on single-nucleotide polymorphism array) and mutations (exome sequence data).


We found approximately 25% of HCCs to have markers of an inflammatory response, with high expression levels of the CD274 molecule (programmed death-ligand 1) and programmed cell death 1, markers of cytolytic activity, and fewer chromosomal aberrations. We called this group of tumors the Immune class. It contained 2 subtypes, characterized by markers of an adaptive T-cell response or exhausted immune response. The exhausted immune response subclass expressed many genes regulated by transforming growth factor beta 1 that mediate immunosuppression. We did not observe any differences in numbers of mutations or expression of tumor antigens between the immune-specific class and other HCCs.


In an analysis of HCC samples from 956 patients, we found almost 25% to express markers of an inflammatory response. We identified 2 subclasses, characterized by adaptive or exhausted immune responses. These findings indicate that some HCCs might be susceptible to therapeutic agents designed to block the regulatory pathways in T cells, such as programmed death-ligand 1, programmed cell death 1, or transforming growth factor beta 1 inhibitors.


Question posée
Evaluation de l’infiltrat inflammatoire intratumoral dans le CHC dans l’hypothèse que ce serait un marqueur prédictif de l’efficacité de l’immunothérapie.
Question posée
25% des tumeurs examinées avaient un infiltrat inflammatoire significatif (expression entre autre de PDL-1 et PD-1).

Résultats à suivre, il n’est pas encore très clair dans les autres cancers que l’expression de PDL-1 ou PD-1 dans la tumeur soit véritablement un facteur prédictif de l’efficacité de l’immunothérapie (Ac anti PDL-1 ou anti PD1).