Single cell atlas of kidney cancer endothelial cells reveals distinct expression profiles and phenotypes

Yuexin Xu ¹, Chris P Miller ², Jun Xue ^3,4

⁰Translational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, WA, USA. yxu2@fredhutch.org.

Bjc Reports +

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November 8, 2024

View abstract on PubMed

Summary

Tumor endothelial cells (TECs) in clear cell renal cell carcinoma (ccRCC) have a distinct, shared phenotype. This suggests potential for modulating TECs to enhance immune cell therapies for kidney cancer.

Area Of Science

Oncology
Immunology
Cell Biology

Background

Tumor endothelial cells (TECs) are key in the tumor microenvironment, interacting with immune cells.
Their specific phenotypes in clear cell renal cell carcinoma (ccRCC) are not fully understood.

Purpose Of The Study

To characterize the phenotype of TECs in ccRCC.
To investigate TECs' ex vivo functional properties and interactions with immune cells.

Main Methods

Single-cell RNA-sequencing of tumor and normal endothelial cells (NECs) from ccRCC specimens.
Establishment of paired primary TECs and NECs cultures for functional assays.

Main Results

TECs exhibit a common phenotype with enriched pathways in extracellular matrix regulation, cell-cell communication, and IGF signaling.
This phenotype is conserved across different tumor types, indicating convergent evolution.
Cultured TECs maintain gene expression programs conferring apoptosis resistance and enhanced immune cell adhesion, including to regulatory T-cells.

Conclusions

TECs possess a distinct, stable phenotype across tumor types and in ex vivo culture.
TECs' specific adhesive interactions with immune cells offer therapeutic targets for enhancing kidney cancer immunotherapies.