Clinically-relevant cell cross-talk networks in the lung tumor microenvironment interactome
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. To develop a deeper understanding of the interactions between cells within human lung tumors we performed 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 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 we call the Lung Tumor Microenvironment Interactome (LTMI). Using this resource, we identified and validated a prognostically unfavourable influences of fibroblasts on proliferation of malignant lung adenocarcinoma cells. We also found a favorable association between infiltration of specific immune cells and less aggressive tumor cell behavior. 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.
Date: 24 May 2018, 14:00
Venue: NDM Building, Headington OX3 7FZ
Venue Details: Basement seminar room, TDI
Speaker: Andrew Gentles (Stanford)
Organising department: Ludwig Institute for Cancer Research, Oxford Branch
Organiser: Christina Woodward (Oxford Ludwig Institute, Nuffield Department of Medicine, University of Oxford)
Organiser contact email address: christina.woodward@ludwig.ox.ac.uk
Host: Prof Xin Lu (Ludwig Cancer Research, Oxford Branch)
Part of: Ludwig Institute Seminar Series
Booking required?: Not required
Audience: Members of the University only
Editor: Christina Woodward