Tumor Cell Biodiversity Drives Microenvironmental Reprogramming in Liver Cancer
Menée à partir d'échantillons tumoraux prélevés sur 19 patients atteints d'un cancer du foie et à partir de données génomiques et transcriptomiques portant sur 765 tumeurs hépatiques, cette étude met en évidence une corrélation entre la biodiversité cellulaire de la tumeur, les caractéristiques du microenvironnement tumoral et le pronostic
Cellular diversity in tumors is a key factor for therapeutic failures and lethal outcomes of solid malignancies. Here, we determined the single-cell transcriptomic landscape of liver cancer biospecimens from 19 patients. We found varying degrees of heterogeneity in malignant cells within and between tumors and diverse landscapes of tumor microenvironment (TME). Strikingly, tumors with higher transcriptomic diversity were associated with patient's worse overall survival. We found a link between hypoxia-dependent vascular endothelial growth factor expression in tumor diversity and TME polarization. Moreover, T cells from higher heterogeneous tumors showed lower cytolytic activities. Consistent results were found using bulk genomic and transcriptomic profiles of 765 liver tumors. Our results offer insight into the diverse ecosystem of liver cancer and its impact on patient prognosis.
Cancer Cell , résumé, 2018