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Characterizing Stage-Specific Cellular Dynamics and Microenvironmental Remodeling in Lung Adenocarcinoma by Single-Cell RNA Sequencing

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机构: [1]Laboratory of Allergy and Precision Medicine, Chengdu Institute of Respiratory Health, Affiliated Hospital of Southwest Jiaotong University, The Third People's Hospital of Chengdu, Chengdu, 610031, China. [2]Laboratory of Allergy and Precision Medicine, Chengdu Institute of Respiratory Health, The Third People's Hospital of Chengdu (Affiliated Hospital of Southwest Jiaotong University), College of Medicine, Southwest Jiaotong University, Chengdu, 610031, China. [3]Department of Pulmonary and Critical Care Medicine, Chengdu Third People's Hospital Branch of National Clinical Research Center for Respiratory Disease, Affiliated Hospital of Chongqing Medical University, Chengdu, 610031, China. [4]Department of Thoracic Surgery, Affiliated Hospital of Southwest Jiaotong University, The Third People's Hospital of Chengdu, Chengdu, 610031, China. [5]Clinical Medicine Department, North Sichuan Medical College, Nanchong, 637000, China.
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关键词: hypoxia LUAD single-cell RNA sequencing TME

摘要:
Lung adenocarcinoma (LUAD) progression involves dynamic remodeling of the tumor microenvironment (TME). However, the stage-specific dynamics of immune and stromal cell remodeling throughout LUAD progression remain incompletely understood. Here, the study systematically profiles the cellular composition and transcriptional states across multiple LUAD stages, integrating early-stage patient specimens with publicly available datasets encompassing advanced-stage disease. The analysis reveals a marked stage-dependent shift from a proliferative and immune-activated microenvironment in early LUAD to a hypoxia-enriched and immunosuppressive landscape in advanced disease. A distinct hypoxia-adapted epithelial tumor cell subpopulation (C5), exhibiting transcriptional features of metastasis, invasion, and hypoxia, and poor prognosis, is identified. Advanced LUAD featured immunosuppressive LGMN⁺ macrophages and STAT1-driven exhausted CD8⁺ T cells. FKBP11⁺ plasma B cells exhibited exhaustion-linked metabolic changes. POSTN⁺ CAFs emerged as central mediators of extracellular matrix (ECM) remodeling and immune exclusion. Collectively, the findings reveal a model of hypoxia-driven functional convergence, in which distinct TME components co-evolve toward phenotypes that collectively promote immune evasion, matrix remodeling, and tumor progression. These findings may provide insights into stage-specific cellular dynamics and highlight promising therapeutic targets for precision immunotherapy strategies.© 2025 The Author(s). Advanced Science published by Wiley‐VCH GmbH.

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出版当年[2025]版:
大类 | 1 区 综合性期刊
小类 | 1 区 化学:综合 1 区 材料科学:综合 1 区 纳米科技
最新[2025]版:
大类 | 1 区 综合性期刊
小类 | 1 区 化学:综合 1 区 材料科学:综合 1 区 纳米科技
第一作者:
第一作者机构: [1]Laboratory of Allergy and Precision Medicine, Chengdu Institute of Respiratory Health, Affiliated Hospital of Southwest Jiaotong University, The Third People's Hospital of Chengdu, Chengdu, 610031, China. [2]Laboratory of Allergy and Precision Medicine, Chengdu Institute of Respiratory Health, The Third People's Hospital of Chengdu (Affiliated Hospital of Southwest Jiaotong University), College of Medicine, Southwest Jiaotong University, Chengdu, 610031, China.
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通讯机构: [1]Laboratory of Allergy and Precision Medicine, Chengdu Institute of Respiratory Health, Affiliated Hospital of Southwest Jiaotong University, The Third People's Hospital of Chengdu, Chengdu, 610031, China. [2]Laboratory of Allergy and Precision Medicine, Chengdu Institute of Respiratory Health, The Third People's Hospital of Chengdu (Affiliated Hospital of Southwest Jiaotong University), College of Medicine, Southwest Jiaotong University, Chengdu, 610031, China. [3]Department of Pulmonary and Critical Care Medicine, Chengdu Third People's Hospital Branch of National Clinical Research Center for Respiratory Disease, Affiliated Hospital of Chongqing Medical University, Chengdu, 610031, China.
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