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Resolving the spatial and cellular architecture of intra-tumor heterogeneity by multi-region dissection of lung adenocarcinoma

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摘要Although the spatial characteristics within the tumor microenvironment of lung adenocarcinoma(LUAD)have been identified,the mechanisms by which these factors promote LUAD progression and immune evasion remain unclear.Using spatial transcriptomics and single-cell RNA-sequencing data from multi-regional LUAD biopsies consisting of tumor core,tumor edge,and normal area,we sought to delineate the spatial hetero-geneity and driving factors of cell colocalization.Two cancer cell sub-clusters(Cancer_c1 and Cancer_c2),associated with LUAD initiation and metastasis,respectively,exhibit distinct spatial distributions and immune cell colocalizations.In particular,Cancer_c1,enriched within the tumor core,could directly interact with B cells or indirectly recruit B cells through macrophages.Conversely,Cancer_c2 enriched within the tumor edge exhibits colocalization with CD8+T cells.Collectively,our work elucidates the spatial distribution of cancer cell subtypes and their interaction with immune cells in the core and edge of LUAD,providing insights for developing therapeutic strategies for cancer intervention.

作者 Song Mei ^[1] Xiaolei Wang ^[2] Mengmeng Zhao ^[3] Qing Huang ^[4] Yixuan Huang ^[5] Mingming Su ^[5] Xinlei Zhang ^[5] Xu Wang ^[6] Xueyu Hao ^[7] Tianning Wang ^[3] Yanhua Wu ^[8] Yuanhui Ma ^[2] Jingnan Wang ^[9] Peng Zhang ^[7] Yan Zheng ^[3] 学术成果认领

作者单位 Beijing Key Laboratory for Genetics of Birth Defects,Beijing Pediatric Research Institute,MOE Key Laboratory of Major Diseases in Children,Rare Disease Center,Beijing Children's Hospital,Capital Medical University,National Center for Children's Health,Beijing 100045,China;Shanghai Institute of Immunology,Shanghai Jiao Tong University School of Medicine,Shanghai 200025,China ^[1] Department of Pathology,Shandong Public Health Clinical Center,Shandong University,Jinan,Shandong 250100,China ^[2] Research Center of Translational Medicine,Central Hospital Affiliated to Shandong First Medical University,Jinan,Shandong 250013,China ^[3] Department of Thoracic Surgery,Shandong Public Health Clinical Center,Shandong University,Jinan,Shandong 250100,China ^[4] Beijing ClouDNA Technology Co.,Ltd.,Beijing 100080,China ^[5] School of Medical Technology and Engineering,Fujian Medical University,Fuzhou,Fujian 350122,China ^[6] Beijing Key Laboratory for Genetics of Birth Defects,Beijing Pediatric Research Institute,MOE Key Laboratory of Major Diseases in Children,Rare Disease Center,Beijing Children's Hospital,Capital Medical University,National Center for Children's Health,Beijing 100045,China ^[7] Department of Lab Medicine,Shandong Public Health Clinical Center,Shandong University,Jinan,Shandong 250100,China ^[8] Department of Oncology,Central Hospital Affiliated to Shandong First Medical University,Jinan,Shandong 250013,China ^[9]

关键词 Lung adenocarcinoma Spatial transcriptomics scRNA-seq Intra-tumoral heterogeneity Cell colocalizations

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Original Research

DOI 10.1016/j.jgg.2025.02.006

发布时间 2025-10-21（万方平台首次上网日期，不代表论文的发表时间）

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