CD169+resident macrophages in lymph nodes of breast cancer patients are for unknown reasons associated with a beneficial prognosis. This contrasts CD169+macrophages present in primary breast tumors (CD169+TAMs), that correlate with a worse prognosis. We recently showed that these CD169+TAMs were associated with tertiary lymphoid structures (TLSs) and Tregsin breast cancer. Here, we show that CD169+TAMs can be monocyte-derived and express a unique mediator profile characterized by type I IFNs, CXCL10, PGE2and inhibitory co-receptor expression pattern. The CD169+monocyte-derived macrophages (CD169+Mo-M) possessed an immunosuppressive functionin vitroinhibiting NK, T and B cell proliferation, but enhanced antibody and IL6 secretion in activated B cells. Our findings indicate that CD169+Mo-M in the primary breast tumor microenvironment are linked to both immunosuppression and TLS functions, with implications for future targeted Mo-M therapy.