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Elucidating cellular origins and TME dynamic evolution in NSCLC through multi-omics technologies

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机构： [1]Department of Pulmonary and Critical Care Medicine, Institute of Respiratory Health, State Key Laboratory of Respiratory Health and Multimorbidity, Frontiers Science Center for Disease-related Molecular Network, Sichuan Provincial Engineering Laboratory of Precision Medicine, Precision Medicine Key Laboratory of Sichuan Province, West China Hospital, West China School of Medicine, Sichuan University, Chengdu 610041, Sichuan Province, China.

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关键词： Non-small cell lung cancer Multi-omics Tumor microenvironment Lineage plasticity Immune editing Therapeutic resistance

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Non-small cell lung cancer (NSCLC) is a leading cause of cancer mortality. Despite progress in targeted therapies and immunotherapy, resistance driven by tumor heterogeneity and dynamic tumor microenvironment (TME) remodeling persists. Multi-omics (single-cell/spatial transcriptomics) reveals lung adenocarcinoma (LUAD) origins in alveolar type 2 (AT2) cells and lineage plasticity via SOX2/WNT/YAP pathways driving aggressive subtypes. The TME, a dynamic ecosystem of immune cells and fibroblasts, evolves through immune-editing phases and cancer-associated fibroblasts (CAF)/tumor-associated macrophage (TAM) crosstalk to foster immunosuppression. Multi-omics identifies key immune subsets (CXCL13+CD8+T cells, M1/M2 macrophages) and antigen-presenting cancer-associated fibroblasts (apCAFs) as therapeutic targets. Emerging strategies targeting lineage plasticity, TME reprogramming, and microbiome modulation may overcome immune checkpoint blockade (ICB)/tyrosine kinase inhibitor (TKI) resistance. Challenges in spatiotemporal heterogeneity resolution call for artificial intelligence (AI)-driven TME modeling to guide precision interventions. This review highlights multi-omics in bridging NSCLC evolution with clinical translation for personalized therapies.Copyright © 2025. Published by Elsevier B.V.

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出版当年[2025]版中科院分区表Review为是的期刊

：

大类 | 2 区

医学

小类 | 2 区生化与分子生物学 2 区生物物理 2 区肿瘤学

最新[2025]版

：

大类 | 2 区

医学

小类 | 2 区生化与分子生物学 2 区生物物理 2 区肿瘤学

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第一作者机构： [1]Department of Pulmonary and Critical Care Medicine, Institute of Respiratory Health, State Key Laboratory of Respiratory Health and Multimorbidity, Frontiers Science Center for Disease-related Molecular Network, Sichuan Provincial Engineering Laboratory of Precision Medicine, Precision Medicine Key Laboratory of Sichuan Province, West China Hospital, West China School of Medicine, Sichuan University, Chengdu 610041, Sichuan Province, China.

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