WCLC 2025 - Posters & ePosters-EP.03.14 Single-Cell Transcriptome Analysis Revealed an Activated Tumor Immune Microenvironment in KRAS Mutant NSCLC

EP.03.14 Single-Cell Transcriptome Analysis Revealed an Activated Tumor Immune Microenvironment in KRAS Mutant NSCLC

Pdf Summary

This study investigates the tumor immune microenvironment (TME) in KRAS-mutant (mKRAS) non-small cell lung cancer (NSCLC) using single-cell transcriptome analysis and clinical data. KRAS mutations, particularly G12D (38.3%) and G12C (31.9%), are common in NSCLC and associated with poor prognosis. Immunotherapy is a more effective first-line treatment compared to chemotherapy for mKRAS NSCLC patients, as evidenced by a median progression-free survival (PFS) of 9.10 months versus 5.63 months, respectively (P=0.030, HR=0.467).<br /><br />Single-cell RNA sequencing from 10 mKRAS and 13 wild-type KRAS (wtKRAS) NSCLC samples revealed distinct immune microenvironment differences. mKRAS tumors had significantly increased tumor-infiltrating lymphocytes, including both B and T cells. Immune checkpoint molecules PDCD1, LAG3, and HAVCR2 were enriched in mKRAS cases. Notably, tissue resident memory CD8+ T cells (CD8 TRM) and naïve CD8+ T cells were predominant in mKRAS tumors, while regulatory CD4+ T cells (Tregs) were more dominant in wtKRAS tumors.<br /><br />The enrichment of CD8 TRM cells and reduction of CD4 Tregs in mKRAS NSCLC may underlie an activated and potentially more immunologically responsive tumor microenvironment. These findings improve understanding of the immune landscape in mKRAS NSCLC and support the potential for targeted immunotherapy strategies.<br /><br />In summary, the study highlights that mKRAS NSCLC features an activated TME characterized by increased cytotoxic CD8+ T cell populations and immune checkpoint expression, contributing to better responses to immunotherapy and improved patient outcomes compared to chemotherapy.

Asset Subtitle

Hao Wang

Meta Tag

Speaker Hao Wang

Topic Tumor Biology – Translational Biology

Keywords

KRAS-mutant NSCLC

tumor immune microenvironment

single-cell transcriptome analysis

immunotherapy

progression-free survival

tumor-infiltrating lymphocytes

immune checkpoint molecules

CD8+ tissue resident memory T cells

regulatory CD4+ T cells

cytotoxic T cell populations