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.
journal_name
Genome Bioljournal_title
Genome biologyauthors
Gentles AJ,Hui AB,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 SKdoi
10.1186/s13059-020-02019-xsubject
Has Abstractpub_date
2020-05-07 00:00:00pages
107issue
1eissn
1474-7596issn
1474-760Xpii
10.1186/s13059-020-02019-xjournal_volume
21pub_type
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