biostudies-literatureZhang RNational Natural Science Foundation of China97https://www.ebi.ac.uk/biostudies/studies/S-EPMC9977784biostudies-literatureUnknown8(1)Our previous studies have showed that C-C motif chemokine ligand 20 (CCL20) advanced tumor progression and enhanced the chemoresistance of cancer cells by positively regulating breast cancer stem cell (BCSC) self-renewal. However, it is unclear whether CCL20 affects breast cancer progression by remodeling the tumor microenvironment (TME). Here, we observed that polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) were remarkably enriched in TME of CCL20-overexpressing cancer cell orthotopic allograft tumors. Mechanistically, CCL20 activated the differentiation of granulocyte-monocyte progenitors (GMPs) via its receptor C-C motif chemokine receptor 6 (CCR6) leading to the PMN-MDSC expansion. PMN-MDSCs from CCL20-overexpressing cell orthotopic allograft tumors (CCL20-modulated PMN-Signal transduction and targeted therapyPMN-MDSCs modulated by CCL20 from cancer cells promoted breast cancer cell stemness through CXCL2-CXCR2 pathway.PMC99777848207326781930075Li FDeng QDong MZhang LLiu STu JDing JChang ZZhang RSheng DXu JMa WXia JDong HZhang YHe XfalsePMN-MDSCs modulated by CCL20 from cancer cells promoted breast cancer cell stemness through CXCL2-CXCR2 pathway.Our previous studies have showed that C-C motif chemokine ligand 20 (CCL20) advanced tumor progression and enhanced the chemoresistance of cancer cells by positively regulating breast cancer stem cell (BCSC) self-renewal. However, it is unclear whether CCL20 affects breast cancer progression by remodeling the tumor microenvironment (TME). Here, we observed that polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) were remarkably enriched in TME of CCL20-overexpressing cancer cell orthotopic allograft tumors. Mechanistically, CCL20 activated the differentiation of granulocyte-monocyte progenitors (GMPs) via its receptor C-C motif chemokine receptor 6 (CCR6) leading to the PMN-MDSC expansion. PMN-MDSCs from CCL20-overexpressing cell orthotopic allograft tumors (CCL20-modulated PMN-2023-01-01T00:00:00Z2023 Mar2025-04-18T14:12:48.536Z2025-04-07T00:13:52.844ZS-EPMC99777843685935410.1038/s41392-023-01337-3