Abstract 6265: Cross-tissue atlas of human disease identifies tumor-specific components in tumor microenvironment

Abstract Human diseases affect various cell types within the local niche, but the multicellular responses of human diseases have not been collectively assessed across organs. Here, we categorize multicellular responses of human diseases based on a remapped human cell atlas, incorporating 12 million single-cell transcriptome profiles acquired from an automated data collection pipeline. Additional curation expands the collection up to 46 million cells, covering 160 disease conditions across 49 distinct organ identities. From the re-aligned atlas of single-cell transcriptome data, we constructed a hierarchical cell classification framework comprising 32 major cell types and 165 cell subtype annotations. Systematic profiling of disease and organ association patterns of cellular subtype reveals archetypes of human diseases repeatedly found across organs, including a multicellular phenotype highly specific to the tumor microenvironment. The universal cell atlas could serve as a reference for unbiased deconvolution of spatial transcriptome datasets, revealing spatial distribution patterns associated with immunotherapy responses. Collectively, our study provides foundational resources for cross-tissue cell type annotation, presents a comprehensive multicellular overview of disease-associated responses across human tissues, and highlights multicellular responses in tumor microenvironments. Citation Format: Seongryong Kim, Sungmin Cheong, Suho Lee, Yeju Kim, Jong-Eun Park. Cross-tissue atlas of human disease identifies tumor-specific components in tumor microenvironment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6265.