Cancer Cell
Volume 36, Issue 4, 14 October 2019, Pages 418-430.e6
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Article
Tumor Cell Biodiversity Drives Microenvironmental Reprogramming in Liver Cancer

https://doi.org/10.1016/j.ccell.2019.08.007Get rights and content
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Highlights

  • HCC and iCCA have a varying degree of transcriptomic diversity

  • Tumor transcriptomic diversity is associated with patient outcomes

  • Tumor-derived VEGF drives microenvironmental reprogramming

  • T cells derived from higher heterogeneous tumors showed lower cytolytic activities

Summary

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.

Keywords

liver cancer
hepatocellular carcinoma
cholangiocarcinoma
single-cell
tumor heterogeneity
tumor microenvironments
VEGF
microenvironmental reprogramming
biodiversity
tumor ecosystem

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