A human lung tumor microenvironment interactome identifies clinically relevant cell-type cross-talk

Area of Science:

• Oncology
• Molecular Biology
• Bioinformatics

Background:

• Tumors feature complex microenvironments with interacting malignant and stromal cells.
• Current understanding often relies on simplified in vitro models studying single cell-type interactions.

Purpose of the Study:

• To deepen the understanding of cell-cell interactions within human lung tumors.
• To create a comprehensive resource for studying the lung tumor microenvironment.

Main Methods:

• RNA-sequencing (RNA-seq) profiling of flow-sorted cells (malignant, endothelial, immune, fibroblasts) from primary non-small cell lung tumors.
• Computational reconstruction of cell-cell communication networks.
• Development of the Lung Tumor Microenvironment Interactome (LTMI) resource.

Main Results:

• Identified cell-specific differential expression of secreted and cell surface genes.
• Validated an unfavorable prognostic influence of fibroblast-derived Gremlin-1 on lung adenocarcinoma cell proliferation.
• Observed a favorable association between mast cell infiltration and less aggressive tumor behavior.

Conclusions:

• The Lung Tumor Microenvironment Interactome (LTMI) is a valuable resource for generating hypotheses on tumor-microenvironment interactions.
• Findings highlight potential prognostic and therapeutic targets within the lung tumor microenvironment.