CXCR2 Small-Molecule Antagonist Combats Chemoresistance and Enhances Immunotherapy in Triple-Negative Breast Cancer.

ABSTRACT: Triple-negative breast cancer (TNBC) is the most malignant subtype of breast cancer as the absence of cell surface receptors renders it more difficult to be therapeutically targeted. Chemokine receptor 2 (CXCR2) has been suggested not only to promote therapy resistance and suppress immunotherapy but it also to possess a positive cross-talk with the multifunctional cytokine transforming growth factor beta (TGF-β). Here, we showed that CXCR2 and TGF-β signaling were both upregulated in human TNBC biopsies. CXCR2 inhibition abrogated doxorubicin-mediated TGF-β upregulation in 3D in vitro TNBC coculture with PBMCs and eliminated drug resistance in TNBC mammospheres, suggesting a vital role for CXCR2 in TNBC doxorubicin-resistance via TGF-β signaling regulation. Moreover, CXCR2 in

SUBMITTER: Ghallab AM 

PROVIDER: S-EPMC9065340 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature