Single-cell and bulk transcriptomic characterization of the osteosarcoma microenvironment reveals lineage-specific programs and inflammatory differences associated with metastasis.

In primary osteosarcoma single-cell RNA-seq (GSE162454; six patients), myeloid cells (34.0%) and osteoblasts (16.6%) show distinct inflammatory versus osteogenic programs, with strongest ligand-receptor scores including MIF-CD74.

• Why it matters: Immune-checkpoint blockade has limited clinical activity in advanced osteosarcoma, and cross-sectional transcriptomics can mislead without cell-type-resolved microenvironment mapping.
• What they did: Single-cell data were processed in Scanpy to retain 44,189 cells (25,473 genes), identify 23 Leiden clusters across 11 cell types, and score seven transcriptional programs plus ligand-receptor interactions; bulk validation used GSE21257 (n = 53).
• The result: In GSE21257, 333 genes differed between metastatic and non-metastatic tumors (FDR<0.05), with a lower inflammatory module in metastatic disease, but osteoblast-centered signatures showed limited concordance (Spearman rho = 0.254) and did not stratify survival (log-rank p = 0.968).

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