Cancer-associated fibroblast heterogeneity in chordoma^†

Area of Science:

• Oncology
• Cancer Biology
• Tumor Microenvironment

Background:

• Malignant cells in solid tumors interact with stromal cells for growth and support.
• Chordoma, a rare bone tumor, exhibits complex cellular interactions within its microenvironment.

Purpose of the Study:

• To comprehensively characterize the cellular landscape of chordoma.
• To identify and define specific cancer-associated fibroblast (CAF) subtypes and their prognostic significance in chordoma.

Main Methods:

• Utilized single-cell and spatial transcriptomics to analyze chordoma tissue.
• Catalogued cellular populations, including malignant cells and stromal components like CAFs.

Main Results:

• Chordoma cells display a mixed phenotype, expressing epithelial, mesenchymal, partial epithelial-to-mesenchymal transition (EMT), and stem-cell signatures.
• Identified a novel inflammatory CAF (iCAF) subtype associated with poor outcomes and increased tumor invasion.
• Proposed that iCAFs originate from normal fibroblasts and drive an aggressive tumor phenotype.

Conclusions:

• Chordoma exhibits significant cellular heterogeneity, with malignant cells retaining epithelial markers despite their mesenchymal origin.
• The identified iCAF subtype represents a potential therapeutic target, but further research is needed to establish causality.
• Integrating findings across studies is crucial for a consensus on chordoma's cellular landscape and for comparing CAFs across different tumor types.