Frontiers in Immunology (Jun 2023)

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

  • Frida Björk Gunnarsdottir,
  • Oscar Briem,
  • Aida Yifter Lindgren,
  • Eva Källberg,
  • Cajsa Andersen,
  • Robert Grenthe,
  • Cassandra Rosenqvist,
  • Camilla Rydberg Millrud,
  • Mika Wallgren,
  • Hannah Viklund,
  • Daniel Bexell,
  • Martin E. Johansson,
  • Ingrid Hedenfalk,
  • Catharina Hagerling,
  • Catharina Hagerling,
  • Karin Leandersson

DOI
https://doi.org/10.3389/fimmu.2023.1180209
Journal volume & issue
Vol. 14

Abstract

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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 Tregs 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.

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