WCLC 2025 - Posters & ePosters-P2.02.38 Single-Cell RNA-Sq Reveals Potential Mechanism of RUNx3 Reshaping TME in NSCLC

Pdf Summary

This study investigates how RUNX3, a tumor suppressor gene, influences the tumor microenvironment (TME) in non-small cell lung cancer (NSCLC) by utilizing single-cell RNA sequencing. Among seven NSCLC patients, samples were categorized into RUNX3 positive (RUNX3_Pos) and RUNX3 negative (RUNX3_Neg) groups based on immunohistochemical staining. Using bioinformatics tools, 13 cell types were identified in tumor tissues.<br /><br />Key findings reveal significant differences in TME composition between RUNX3_Pos and RUNX3_Neg tumors. RUNX3_Pos tumors demonstrated enrichment primarily of fibroblasts, while RUNX3_Neg tumors were enriched with diverse immune and stromal cell types including club cells, ciliated cells, plasma cells, B cells, neutrophils, mast cells, and plasmacytoid dendritic cells. Notably, immune profiles differed with RUNX3_Neg tissues showing higher accumulation of plasma cells, B cells, mast cells, and plasmacytoid dendritic cells compared to RUNX3_Pos tissues. Additionally, RUNX3_Pos tumors exhibited a tendency toward macrophage enrichment, whereas RUNX3_Neg tumors showed macrophage depletion.<br /><br />These results suggest that RUNX3 expression modulates the immune landscape of NSCLC, particularly affecting mononuclear phagocytes (MPs) such as macrophages, which may be a critical mediator in remodeling the TME. Consequently, targeting MPs could represent a promising therapeutic strategy.<br /><br />The authors propose future research involving RUNX3 gene knockout (KO) or knock-in (KI) models in animals or organoids to further validate RUNX3’s role in shaping TME dynamics in NSCLC.<br /><br />In summary, this study provides valuable insights into how RUNX3 status alters the NSCLC tumor microenvironment, emphasizing its potential as a target to modulate immune cell populations for improved cancer treatment outcomes.

Asset Subtitle

Xiaohui Chen

Meta Tag

Speaker Xiaohui Chen

Topic Tumor Biology – Preclinical Biology

Keywords

RUNX3

tumor microenvironment

non-small cell lung cancer

single-cell RNA sequencing

immunohistochemical staining

fibroblasts

immune cell types

macrophages

mononuclear phagocytes

cancer immunotherapy