Understanding tumour endothelial cell heterogeneity and function from single-cell omics.

Area of Science:

• Oncology
• Cell Biology
• Immunology

Background:

• Anti-angiogenic therapies (AATs) are crucial cancer treatments but face challenges with efficacy and resistance.
• Single-cell omics studies have begun to elucidate the complex biology of tumor endothelial cells (TECs).

Purpose of the Study:

• To provide a comprehensive overview of human TEC heterogeneity across various tumor types at the single-cell level.
• To identify universal TEC markers and explore their biological functions beyond angiogenesis.
• To discuss novel therapeutic strategies for AAT development, considering TEC immunomodulatory properties.

Main Methods:

• Analysis of single-cell omics data from human tumor endothelial cells (TECs) across multiple tumor types.
• Identification and comparison of TEC phenotypes and universal markers.
• Bioinformatic prediction of enriched biological processes in TECs.

Main Results:

• TECs exhibit significant heterogeneity within and across tumor types, with only a small population of angiogenic TECs identified.
• Universal TEC markers (ACKR1, PLVAP, IGFBP3) were identified across most tumor types.
• Immunomodulation and extracellular matrix organization were common enriched functions in TECs, alongside angiogenesis.

Conclusions:

• The heterogeneity of TECs, particularly the limited angiogenic population, may explain AAT resistance.
• A lack of standardized nomenclature and analysis protocols hinders cross-tumor TEC comparisons.
• Targeting TEC immunomodulatory functions presents a promising, yet underexplored, avenue for novel anti-cancer therapeutic strategies.