ETS1-Driven Nucleolar Stress Orchestrates OLR1⁺ Macrophage Crosstalk to Sustain Immunosuppressive Microenvironment in Clear Cell Renal Cell Carcinoma.

ABSTRACT: While hypoxia-driven nucleolar stress (NS) has been recognized as a critical modulator of the immunosuppressive tumor microenvironment in clear cell renal cell carcinoma (ccRCC), its mechanistic contribution to disease progression remains poorly defined. To address this gap, we systematically mapped NS-associated molecular landscapes through integrated spatial transcriptomics and single-cell RNA sequencing of ccRCC specimens. Our analysis stratified tumors into two distinct NS subtypes, revealing that high-NS tumors exhibit aggressive clinical behavior, elevated expression of immunosuppressive checkpoints, and significantly reduced survival. At single-cell resolution, high-NS malignant cells displayed enhanced proliferative activity, glycolytic metabolic reprograming, and marked chromosoma

SUBMITTER: Xiao L 

PROVIDER: S-EPMC12513783 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature