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Characterizing Stage-Specific Cellular Dynamics and Microenvironmental Remodeling in Lung Adenocarcinoma by
Bomiao Qing1,2, Xiaolan Li1,2, Xiang He1,2,3
1Laboratory 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.
Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|November 28, 2025
Summary
Tumor microenvironment in lung adenocarcinoma (LUAD) shifts from immune-activated to immunosuppressive with disease progression. Hypoxia drives this change, promoting tumor invasion and immune evasion, offering new therapeutic targets.
Area of Science:
- Oncology
- Immunology
- Cell Biology
Background:
- Lung adenocarcinoma (LUAD) progression involves complex tumor microenvironment (TME) remodeling.
- Stage-specific immune and stromal cell dynamics in LUAD progression are not fully understood.
Purpose of the Study:
- To systematically profile cellular composition and transcriptional states across LUAD stages.
- To elucidate stage-dependent TME remodeling and identify key drivers of LUAD progression.
Main Methods:
- Integration of early-stage patient specimens with advanced-stage public datasets.
- Comprehensive profiling of cellular composition and transcriptional states.
- Bioinformatic analysis to identify stage-specific cellular dynamics and molecular features.
Main Results:
- A stage-dependent shift from immune-activated to hypoxia-enriched, immunosuppressive TME in LUAD.
- Identification of a hypoxia-adapted tumor cell subpopulation (C5) linked to metastasis, invasion, and poor prognosis.
- Characterization of immunosuppressive macrophages, exhausted T cells, B cells, and CAFs mediating ECM remodeling and immune exclusion.
Conclusions:
- Hypoxia drives functional convergence in the TME, promoting immune evasion and tumor progression in advanced LUAD.
- Findings reveal stage-specific TME dynamics and highlight potential therapeutic targets for precision immunotherapy.
