Early lung carcinogenesis and tumor microenvironment observed by single-cell transcriptome analysis.

Area of Science:

• Oncology
• Immunology
• Molecular Biology

Background:

• Ground-glass nodules (GGNs) are common lung lesions detected via chest CT screening.
• Lung adenocarcinoma presenting as GGNs offer a model for studying early lung carcinogenesis.

Purpose of the Study:

• To investigate molecular and cellular changes in early lung adenocarcinoma from never-smokers.
• To identify potential therapeutic targets by analyzing cancer cell biomarkers and the tumor microenvironment (TME).

Main Methods:

• Single-cell RNA sequencing was performed on 11 GGN and normal lung specimens from 6 never-smoker patients.
• Analysis focused on gene expression in cancer cells, fibroblasts, and immune cells within the TME.

Main Results:

• Lung cancer cells exhibited enrichment in small vesicle processing and surfactant homeostasis pathways.
• The TME was characterized by regulatory T cells (Tregs) infiltration and a depletion of cytotoxic T cells (TCs).
• CXCL13 was overexpressed in intratumoral Tregs and CD4+ memory TCs, correlating with B cell presence.

Conclusions:

• Dysregulation of the surfactant pathway may contribute to early lung carcinogenesis.
• Tregs dominate the TME from the onset of lung cancer, orchestrating immune evasion.
• Understanding these early changes provides insights into novel therapeutic targets for lung cancer treatment.