Nuclear PD-L1 drives IFN-γ-promoted lung metastasis of triple-negative breast cancer via POLR2A-mediated transcriptional activation of LY6E.

ABSTRACT:

Background

​​Triple-negative breast cancer (TNBC) patients exhibiting high PD-L1 expression demonstrate poor responses to anti-PD-L1 therapy and aggressive lung metastasis. The paradoxical role of PD-L1 beyond its immune checkpoint function and the impact of interferon-γ-secreted during immunotherapy-on metastasis remain poorly understood.

Methods

Integrated reanalysis of single-cell RNA sequencing (scRNA-seq) data from TNBC lung metastases identified enriched signaling pathways. IFN-γ function was assessed using murine and human TNBC cell lines, employing in vitro assays and in vivo modeling in both immunocompetent and immunodeficient mice. CRISPR/Cas9-mediated PD-L1 ablation, pharmacological inhibitors, RNA sequencing (RNA-seq), chromatin immunoprecipitation sequencing (Ch

SUBMITTER: Wang X 

PROVIDER: S-EPMC12817839 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature