Breast cancer associated CD169 + macrophages possess broad immunosuppressive functions but enhance antibody secretion by activated B cells.

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 T in breast cancer. Here, we show that CD169 TAMs can be monocyte-derived and express a unique mediator profile characterized by type I IFNs, CXCL10, PGE and inhibitory co-receptor expression pattern. The CD169 monocyte-derived macrophages (CD169 Mo-M) possessed an immunosuppressive function inhibiting 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.