Tumor-stroma contributes to immunotherapeutic resistance in non-small cell lung cancer via SEMA3C-mediated immunosuppressive tumor microenvironment.

ABSTRACT:

Background

The tumor-stroma proportion (TSP) was a critical factor influencing clinical outcomes in non-small cell lung cancer (NSCLC). However, the underlying molecular mechanisms driving TSP-associated aggressiveness and its contribution to immune checkpoint blockade (ICB) resistance remained poorly understood.

Methods

Using H&E staining data from the TCGA-NSCLC cohort, patients were stratified into TSP-high and low groups. Transcriptomic profiling and single-cell RNA sequencing (scRNA-seq) were employed to identify the TSP signatures. Functional validation was conducted to investigate the role of SEMA3C in cancer-associated fibroblasts (CAFs) and its influence to tumor cells and T cells.

Results

TSP-high status independently predicted worse overall survival (OS) an

SUBMITTER: Zhang H 

PROVIDER: S-EPMC12857187 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature