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A human lung tumor microenvironment interactome identifies clinically relevant cell-type cross-talk
- A human lung tumor microenvironment interactome identifies clinically relevant cell-type cross-talk
- Gentles, Andrew J.; Hui, Angela Bik-Yu; Feng, Weiguo; Azizi, Armon; Nair, Ramesh, V; Bouchard, Gina; Knowles, David A.; Yu, Alice; Jeong, Youngtae; Bejnood, Alborz; Forgo, Erna; Varma, Sushama; Xu, Yue; Kuong, Amanda; Nair, Viswam S.; West, Rob; van de Rijn, Matt; Hoang, Chuong D.; Diehn, Maximilian; Plevritis, Sylvia K.
- DGIST Authors
- Jeong, Youngtae
- Issue Date
- Genome Biology, 21(1), 107
- Article Type
- TRANSCRIPTIONAL NETWORK; PROGNOSTIC VALUE; GROWTH-FACTOR; CANCER; ANGIOGENESIS; EXPRESSION; MUTATIONS; INFILTRATION; FIBROBLASTS; MODULATORS
- 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. © 2020 The Author(s).
- BioMed Central Ltd.
- Related Researcher
Lab of Stem Cell Biology & Cancer Precision Medicine
Stem cells, Cancer, Precision medicine, Regenerative medicine, Nrf2, antioxidant
- Department of New BiologyLab of Stem Cell Biology & Cancer Precision Medicine1. Journal Articles
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