Age-based shifts in multicellular community organization and abundance in HPV-Negative Head and Neck Cancer

An age-enriched tumor community in HPV-negative head and neck squamous cell carcinoma links basal-like squamous epithelial states, EMT, matrix-associated myofibroblast-like CAFs, and FOLR2+ macrophages.

• Why it matters: Aging reshapes the tumor microenvironment, but the cellular organization changes behind age-linked cancer risk are not well defined.
• What they did: In a single-cell atlas of 73 HPV-negative HNSCC patients aged 18–91, NMF module discovery and partial correlation networks were used to separate age-driven abundance/organization shifts from broad transcriptional rewiring.
• The result: Cross-dataset validation using TCGA transcriptomes, spatial transcriptomics, and mouse tumor models supports conserved age-associated cell-type correlations and ligand–receptor usage, and highlights MDK as a rare but robust tumor-derived signal tied to stromal remodeling and immunosuppression.

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