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bioRxiv · 10.64898/2026.05.15.725574

Transcriptome-inferred CIN-like fields mark antigen-presentation-low, immune-cold spatial neighborhoods

Dutta, S.
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Abstract

Cancer immune escape is usually interpreted as either a tumor-cell-intrinsic antigen-presentation defect or an immune-cold microenvironment. How these states are spatially arranged relative to chromosomal-instability-like genotype states remains unresolved. Here, spatial transcriptomic, single-cell and clinical transcriptomic analyses show that transcriptome-inferred CIN-like fields mark antigen-presentation-low, immune-cold neighborhoods. Across 14 melanoma tissue sections, the interaction between inferred copy-number-like burden and chromosome-expression deviation was associated with reduced MHC-I antigen-presentation activity after adjustment for tumor state, immune inflammation, technical covariates and spatial coordinates. CIN-high/AP-low spots formed coherent neighborhoods enriched for AP-low neighbors but depleted of immune-high and IFN-high neighbors under block-preserving spatial nulls. Two breast cancer Visium sections reproduced AP-low neighborhood topology, while malignant melanoma single-cell RNA-seq supported a tumor-intrinsic CNA-by-chromosome-deviation association with AP repression. Patient-level TCGA analyses linked the adverse genotype-ecotype score to poor melanoma survival. These results define transcriptome-inferred CIN-like fields as spatial correlates of immune-cold antigen-presentation failure.

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Dutta, S.. 2026-05-20. Transcriptome-inferred CIN-like fields mark antigen-presentation-low, immune-cold spatial neighborhoods. https://doi.org/10.64898/2026.05.15.725574

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