|Publication Type||Journal Article|
|Year of Publication||2020|
|Authors||Gentles, 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|
|Date Published||2020 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 Journal||Genome Biol.|
|Grant List||U01CA154969 / CA / NCI NIH HHS / United States |
U54CA209971 / CA / NCI NIH HHS / United States