Deciphering the heterogeneity and immunosuppressive function of regulatory T cells in osteosarcoma using single-cell...

Area of Science:

• Oncology
• Immunology
• Genomics

Background:

• Osteosarcoma (OS) is an aggressive bone cancer with a poor prognosis.
• The tumor microenvironment (TME) significantly influences OS development and progression.
• Regulatory T cells (Tregs) are implicated in tumor immunosuppression and metastasis, but their role in OS TME is not fully understood.

Purpose of the Study:

• To investigate the role and characteristics of Tregs within the OS TME.
• To identify key signaling pathways and cellular interactions involving Tregs in OS.
• To develop a prognostic model based on Treg-specific genes and predict drug sensitivity in OS.

Main Methods:

• Single-cell RNA sequencing (scRNA-seq) to identify cell populations in OS TME.
• Gene Set Variation Analysis (GSVA) to analyze Treg signaling pathways.
• CellChat and iTALK for cellular communication analysis.
• Prognostic model development using bulk RNA-seq (TARGET and GEO datasets).
• Drug sensitivity prediction (pRRophetic) and immunohistochemistry validation.

Main Results:

• OS samples showed high infiltration of Tregs.
• Tregs in OS TME exhibited activated oxidative phosphorylation, angiogenesis, and mTORC1 pathways.
• Tregs communicated with osteoblastic, endothelial, and myeloid cells via CXCL signaling (CXCL12/CXCR4) and TGFB1, promoting tumor growth.
• A prognostic model based on CD320 and MAF demonstrated high accuracy.
• High Treg-risk OS patients showed sensitivity to sunitinib, sorafenib, and axitinib.

Conclusions:

• Tregs exhibit significant heterogeneity within the OS TME.
• Treg-mediated signaling pathways (CXCL, TGFB1) are crucial for OS progression.
• CD320 and MAF are potential prognostic biomarkers for OS.
• Targeting Tregs or utilizing specific drugs may offer new therapeutic strategies for OS.