Gene Signature-Based Drug Screening Reveals Ponatinib Enhances Immunotherapy Efficacy in Triple-Negative Breast Cancer by Reversing MDSC-Mediated Immunosuppressive Tumor Microenvironment.

ABSTRACT: The infiltration of myeloid-derived suppressor cells (MDSCs) is critical for the establishment of immunosuppressive tumor microenvironment (TME), yet no approved therapies specifically block it. Here, we employed a gene signature-based drug screening approach to identify potential agents for reversing MDSC-mediated immunosuppression in triple-negative breast cancer (TNBC). Transcriptomic analysis of 73,326 tumor samples and 190,588 single cells revealed C-X-C motif ligand 1 (CXCL1) and CXCL2 as the key gene signature of MDSC infiltration. Combining this gene signature with high-throughput sequencing-based high-throughput screening (HTS²), we identified ponatinib as a potential inhibitor of MDSC infiltration. By employing multiple preclinical models, we demonstrated

SUBMITTER: Wang Q 

PROVIDER: S-EPMC12508528 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature