A human lung tumor microenvironment interactome identifies clinically relevant cell-type cross-talk.
Authors | |
Abstract | 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. |
Year of Publication | 2020
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Journal | Genome Biol
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Volume | 21
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Issue | 1
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Pages | 107
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Date Published | 2020 May 07
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ISSN | 1474-760X
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DOI | 10.1186/s13059-020-02019-x
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PubMed ID | 32381040
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Links | |
Grant list | U01CA154969 / CA / NCI NIH HHS / United States
U54CA209971 / CA / NCI NIH HHS / United States
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