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

Abstract

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_regs 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, PGE₂ and inhibitory co-receptor expression pattern. The CD169⁺ monocyte-derived macrophages (CD169⁺ Mo-M) possessed an immunosuppressive function in vitro 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.

Keywords: B cell; CD169; TLS; breast cancer; macrophage; tolerance; type I IFN.