Andrew Gentles
Associate Professor (Research)
BMIR, Stanford University

ABSTRACT:

Tumors comprise a complex microenvironment of interacting malignant and stromal cell types. Much of our knowledge comes from studies isolating the interactions between malignant cells and a single component of the microenvironment, often along a single pathway. We performed RNA-seq profiling of bulk non-small-cell primary human lung tumors as well as flow-sorted malignant cells, endothelial cells, immune cells, and fibroblasts. We mapped the cell-specific differential expression of prognostically-associated secreted factors and cell surface genes, and computationally reconstructed cross-talk between these cell types to generate a novel resource, the Lung Tumor Microenvironment Interactome (Lung TMI). Using this resource, we identified and validated a prognostically significant positive association between production of Gremlin-1 by fibroblasts and proliferation of malignant lung adenocarcinoma cells. We also found a favorable association between infiltration of mast cells and less aggressive tumor cell behavior. These results illustrate the utility of the Lung TMI as a resource for generating hypotheses concerning tumor-microenvironment interactions that may have prognostic and therapeutic relevance.