<scp>IL</scp> ‐6 mediated <scp>CD206</scp> ⁺ <scp>ARG</scp> ‐1 ⁺ tumor associated macrophage polarization induces Treg infiltration in non‐responder luminal A breast cancer

Drug non-responsiveness is the major reason for the poor prognosis of hormonal receptor-positive breast cancer (ER⁺/PR⁺ BCa), particularly the luminal A subtype. However, the underlying mechanism of drug non-responsiveness remains unknown. Flow cytometry and t-SNE analysis followed by ELISA validation of responder and non-responder unveiled lower secretion of IFN-γ, IL-12, and higher levels of IL-6 and TGF-β in CD4⁺ T cells (P < 0.001), CD8⁺ T cells (P < 0.001), FOXP3⁺ Tregs (P < 0.001) and CD206⁺ TAMs (P < 0.001) in non-responders. Treatment of isolated CD206⁺ TAMs with recombinant IL-6 upregulated the expression of ARG-1 (arginase-1) and subsequent increase of TGF-β⁺ Tregs (P < 0.001) and IL-6⁺ Tregs (P < 0.001) in luminal A BCa. Our findings showed IL-6 mediated ARG-1⁺CD206⁺ TAMs polarization induced FOXP3⁺ Tregs infiltration in TME of non-responder in luminal A BCa.