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Genome Biol DOI:10.1186/s13059-020-02019-x

A human lung tumor microenvironment interactome identifies clinically relevant cell-type cross-talk.

Publication TypeJournal Article
Year of Publication2020
AuthorsGentles, AJ, Hui, ABik-Yu, Feng, W, Azizi, A, Nair, RV, Bouchard, G, Knowles, DA, Yu, A, Jeong, Y, Bejnood, A, Forgó, E, Varma, S, Xu, Y, Kuong, A, Nair, VS, West, R, van de Rijn, M, Hoang, CD, Diehn, M, Plevritis, SK
JournalGenome Biol
Date Published2020 May 07

BACKGROUND: Tumors comprise a complex microenvironment of interacting malignant and stromal cell types. Much of our understanding of the tumor microenvironment comes from in vitro studies isolating the interactions between malignant cells and a single stromal cell type, often along a single pathway.

RESULT: To develop a deeper understanding of the interactions between cells within human lung tumors, we perform RNA-seq profiling of flow-sorted malignant cells, endothelial cells, immune cells, fibroblasts, and bulk cells from freshly resected human primary non-small-cell lung tumors. We map the cell-specific differential expression of prognostically associated secreted factors and cell surface genes, and computationally reconstruct cross-talk between these cell types to generate a novel resource called the Lung Tumor Microenvironment Interactome (LTMI). Using this resource, we identify and validate a prognostically unfavorable influence of Gremlin-1 production by fibroblasts on proliferation of malignant lung adenocarcinoma cells. We also find a prognostically favorable association between infiltration of mast cells and less aggressive tumor cell behavior.

CONCLUSION: These results illustrate the utility of the LTMI as a resource for generating hypotheses concerning tumor-microenvironment interactions that may have prognostic and therapeutic relevance.


Alternate JournalGenome Biol.
PubMed ID32381040
Grant ListU01CA154969 / CA / NCI NIH HHS / United States
U54CA209971 / CA / NCI NIH HHS / United States