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.

DNA Damage Pathways Revealed: Despite the dynamic nature of cellular responses, the genetic networks that govern these responses have been mapped primarily as static snapshots. Bandyopadhyay et al. (p. 1385 ; see the Perspective by Friedman and Schuldiner ) report a comparison of large genetic interactomes measured among all yeast kinases, phosphatases, and transcription factors, as the cell responded to DNA damage. The interactomes revealed were highly dynamic structures that changed dramatically with changing conditions. These dynamic interactions reveal genetic relationships that can be more effective than classical “static” interactions (for example, synthetic lethals and epistasis maps) in identifying pathways of interest.

Innate defense regulator RP-182 targets CD206 ^high M2-like macrophages in malignant and noncancerous diseases.