Breast cancer associated CD169+ macrophages possess broad immunosuppressive functions but enhance antibody secretion by activated B cells
Fríða Björk Gunnarsdóttir, Oscar Briem, Aida Yifter Lindgren, Eva Källberg, Cajsa Andersen, Robert Grenthe, Cassandra Rosenqvist, Camilla Rydberg Millrud, Mika Wallgren, Hannah Viklund, Daniel Bexell, Martin Johansson, Ingrid Hedenfalk, Catharina Hagerling, Karin Leandersson
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, PGE 2 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.