ArticleClinical and translational medicine2026
Pan-cancer atlas of cellular architecture reveals a nearest-neighbour distance-associated biomechanical-immune axis involving CD4+ memory T cells.
Article in Clinical and translational medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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1 citing paper in PubMed.
- Pan-cancer atlas of cellular architecture reveals a nearest-neighbour distance-associated biomechanical-immune axis involving CD4+ memory T cells.Clinical and translational medicine · 2026Article
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3 authors.
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Abstract
backgroundThe systematic link between cellular spatial organization and its biomechanical consequences remains a critical knowledge gap in human oncology.
objectiveTo quantitatively map the cellular architecture of solid tumours and elucidate its mechanistic impact on mechanical signalling, immune infiltration, and patient survival.
methodsWe developed a scalable digital pathology framework, processing 7910 H&E whole-slide images across 21 solid tumours. A deep learning pipeline was employed to segment over 4.7 billion nuclei, enabling the calculation of cell density and nearest neighbour distance (NND) as key spatial metrics. To bridge morphology and function, we integrated these metrics with bulk RNA-seq data from 19 TCGA cohorts (n = 7401) using rigorous histological matching. Furthermore, to resolve microenvironmental heterogeneity, we performed unsupervised clustering of over 60 000 T-cell transcriptomes from independent cohorts. These findings were validated through high-resolution Visium-HD spatial transcriptomics to correlate physical proximity with localized gene expression.
resultsWhile tumours exhibited significant heterogeneity, NND, but not cell density, emerged as a primary determinant of biomechanical and immune signatures. A trend-level association was observed between lower NND and higher Hippo/YAP/TAZ pathway activity across nine matched cancer types (Spearman's ρ = -.65, p = .058, n = 9). In addition, lower NND was significantly correlated with increased CD4
conclusionOur study identifies low NND as a spatial correlate of biomechanical crowding that is associated with CD4
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