Researchers from the VIB Center for Cancer Biology, Leuven University and University Hospital Leuven (all Belgium) have created the first comprehensive atlas of lung tumor cells. The findings were recently published in Nature Medicine.
To create the atlas, the researchers used single-cell RNAseq technology to study approximately 100,000 individual cells; focusing on both cancerous cells and non-cancerous cells in tumors such as blood vessels, immune cells and fibrous cells.
The atlas comprises a 52,698-cell catalog of the TME transcriptome in human lung tumors at single-cell resolution, validated in independent samples where 40,250 additional cells were sequenced.
Many of the cells studied in the tumors have never before been characterized in their native environments. As the team analyzed both tumor cells and lung cells found outside the tumor and compared the two, they were able to observe how each cell type is altered by the tumor to reveal a highly complex tumor microenvironment that profoundly molds stromal cells.
The team identified 52 stromal cell subtypes, including novel subpopulations in cell types hitherto considered to be homogeneous, as well as transcription factors underlying their heterogeneity.
For example, they identified fibroblasts expressing different collagen sets, endothelial cells downregulating immune cell homing and genes coregulated with established immune checkpoint transcripts and correlating with T-cell activity.
The team also assessed marker genes for these cell subtypes in bulk RNA-sequencing data from 1572 patients, which allowed them to illustrate how these correlate with survival; while immunohistochemistry for selected markers validated them as separate cellular entities in an independent series of lung tumors.
“We were surprised to discover that there are actually many more different cell types in lung tumors than expected. We identified 52 different types of cells, versus the dozen cells already known to be present. This indicates that tumors are even more complex than we had realized,” first author Diether Lambrechts (VIB-KU Leuven, Belgium), commented.
The team believe that this atlas will provide deeper insights into lung cancer biology and that it could be helpful in advancing lung cancer diagnosis and therapy.
“The new information that we’ve gathered will be used to develop new strategies to fight the formation of blood vessels in tumors and to test new potential targets for immunotherapy. In addition, we also demonstrated that the presence of some types of cells is associated with lower patient survival, further emphasizing the clinical importance of our findings,” study author Els Wauters, from Leuven University Hospitals, concluded.
Sources: Lambrechts D, Wauters E, Boeckx B et al. Phenotype molding of stromal cells in the lung tumor microenvironment Nature Med. https://doi.org/10.1038/s41591-018-0096-5 (2018) (Epub ahead of print); www.eurekalert.org/pub_releases/2018-07/vfi-sca070918.php