Decoding Spatiotemporal Microenvironmental Changes in Oral Carcinogenesis

Area of Science:

• Oncology
• Immunology
• Cell Biology

Background:

• Oral carcinogenesis is a multistage process involving epithelial changes and critical microenvironment alterations.
• Understanding these dynamic microenvironmental shifts is key to preventing oral cancer progression.

Purpose of the Study:

• To investigate microenvironment remodeling during oral mucosa carcinogenesis using multi-omics spatiotemporal analysis.
• To identify key cellular players and signaling pathways involved in oral cancer development.

Main Methods:

• Multi-omics spatiotemporal analysis of oral mucosa during carcinogenesis.
• Identification and characterization of oral epithelial progenitor cells (OEPCs) and regulatory B cells (Bregs).
• Spatial transcriptomics to confirm cell proximity and interactions via the TGF-β signaling pathway.

Main Results:

• A subset of OEPCs with high Insulin-like Growth Factor Binding Protein 2 (IGFBP2) expression was identified, showing increased proliferation and reduced differentiation.
• Increasing infiltration of Bregs was observed during precancerous stages, interacting with IGFBP2-high OEPCs through TGF-β signaling.
• Breg infiltration plateaued or declined in advanced cancer, suggesting stage-specific regulatory mechanisms.

Conclusions:

• The study reveals the evolution of the oral cancer microenvironment, highlighting the role of Bregs and IGFBP2-high OEPCs.
• The interaction between Bregs and OEPCs via TGF-β signaling contributes to disrupted cellular balance and potential malignancy.
• Focusing on precancerous stages is crucial for understanding and potentially intervening in oral carcinogenesis.