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

Gunnarsdottir, Frida Björk LU ; Briem, Oscar LU ; Lindgren, Aida Yifter LU ; Källberg, Eva LU ; Andersen, Cajsa ; Grenthe, Robert ; Rosenqvist, Cassandra ; Rydberg Millrud, Camilla LU ; Wallgren, Mika and Viklund, Hannah , et al. (2023) In Frontiers in Immunology 14.
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 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... (More)

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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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
B cell, breast cancer, CD169, macrophage, TLS, tolerance, type I IFN
in
Frontiers in Immunology
volume
14
article number
1180209
publisher
Frontiers Media S. A.
external identifiers
  • pmid:37404831
  • scopus:85163983443
ISSN
1664-3224
DOI
10.3389/fimmu.2023.1180209
language
English
LU publication?
yes
id
a7f4ed12-9b9a-4e08-9d01-ec6703121b32
date added to LUP
2023-10-16 14:06:48
date last changed
2024-04-19 02:23:46
@article{a7f4ed12-9b9a-4e08-9d01-ec6703121b32,
  abstract     = {{<p>CD169<sup>+</sup> resident macrophages in lymph nodes of breast cancer patients are for unknown reasons associated with a beneficial prognosis. This contrasts CD169<sup>+</sup> macrophages present in primary breast tumors (CD169<sup>+</sup> TAMs), that correlate with a worse prognosis. We recently showed that these CD169<sup>+</sup> TAMs were associated with tertiary lymphoid structures (TLSs) and T<sub>regs</sub> in breast cancer. Here, we show that CD169<sup>+</sup> TAMs can be monocyte-derived and express a unique mediator profile characterized by type I IFNs, CXCL10, PGE<sub>2</sub> and inhibitory co-receptor expression pattern. The CD169<sup>+</sup> monocyte-derived macrophages (CD169<sup>+</sup> 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<sup>+</sup> Mo-M in the primary breast tumor microenvironment are linked to both immunosuppression and TLS functions, with implications for future targeted Mo-M therapy.</p>}},
  author       = {{Gunnarsdottir, Frida Björk and Briem, Oscar and Lindgren, Aida Yifter and Källberg, Eva and Andersen, Cajsa and Grenthe, Robert and Rosenqvist, Cassandra and Rydberg Millrud, Camilla and Wallgren, Mika and Viklund, Hannah and Bexell, Daniel and Johansson, Martin E. and Hedenfalk, Ingrid and Hagerling, Catharina and Leandersson, Karin}},
  issn         = {{1664-3224}},
  keywords     = {{B cell; breast cancer; CD169; macrophage; TLS; tolerance; type I IFN}},
  language     = {{eng}},
  publisher    = {{Frontiers Media S. A.}},
  series       = {{Frontiers in Immunology}},
  title        = {{Breast cancer associated CD169<sup>+</sup> macrophages possess broad immunosuppressive functions but enhance antibody secretion by activated B cells}},
  url          = {{http://dx.doi.org/10.3389/fimmu.2023.1180209}},
  doi          = {{10.3389/fimmu.2023.1180209}},
  volume       = {{14}},
  year         = {{2023}},
}