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CD169+ Macrophages in Primary Breast Tumors Associate with Tertiary Lymphoid Structures, Tregs and a Worse Prognosis for Patients with Advanced Breast Cancer

Briem, Oscar LU ; Källberg, Eva LU ; Kimbung, Siker LU ; Veerla, Srinivas LU orcid ; Stenström, Jenny ; Hatschek, Thomas ; Hagerling, Catharina LU ; Hedenfalk, Ingrid LU orcid and Leandersson, Karin LU orcid (2023) In Cancers 15(4).
Abstract

The presence of CD169+ macrophages in the draining lymph nodes of cancer patients is, for unknown reasons, associated with a beneficial prognosis. We here investigated the prognostic impact of tumor-infiltrating CD169+ macrophages in primary tumors (PTs) and their spatial relation to tumor-infiltrating B and T cells. Using two breast cancer patient cohorts, we show that CD169+ macrophages were spatially associated with the presence of B and T cell tertiary lymphoid-like structures (TLLSs) in both PTs and lymph node metastases (LNMs). While co-infiltration of CD169+/TLLS in PTs correlated with a worse prognosis, the opposite was found when present in LNMs. RNA sequencing of breast tumors... (More)

The presence of CD169+ macrophages in the draining lymph nodes of cancer patients is, for unknown reasons, associated with a beneficial prognosis. We here investigated the prognostic impact of tumor-infiltrating CD169+ macrophages in primary tumors (PTs) and their spatial relation to tumor-infiltrating B and T cells. Using two breast cancer patient cohorts, we show that CD169+ macrophages were spatially associated with the presence of B and T cell tertiary lymphoid-like structures (TLLSs) in both PTs and lymph node metastases (LNMs). While co-infiltration of CD169+/TLLS in PTs correlated with a worse prognosis, the opposite was found when present in LNMs. RNA sequencing of breast tumors further confirmed that SIGLEC1 (CD169) expression was associated with mature tertiary lymphoid structure (TLS), and Treg and Breg signatures. We propose that the negative prognostic value related to CD169+ macrophages in PTs is a consequence of an immunosuppressive tumor environment rich in TLSs, Tregs and Bregs.

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author
; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
B, breast cancer, CD169, lymph node, macrophage, T, TLS
in
Cancers
volume
15
issue
4
article number
1262
publisher
MDPI AG
external identifiers
  • scopus:85149113931
  • pmid:36831605
ISSN
2072-6694
DOI
10.3390/cancers15041262
language
English
LU publication?
yes
id
78a25819-d7bb-4871-97dd-cbbd18aa5836
date added to LUP
2023-03-20 12:24:19
date last changed
2025-05-04 11:40:54
@article{78a25819-d7bb-4871-97dd-cbbd18aa5836,
  abstract     = {{<p>The presence of CD169<sup>+</sup> macrophages in the draining lymph nodes of cancer patients is, for unknown reasons, associated with a beneficial prognosis. We here investigated the prognostic impact of tumor-infiltrating CD169<sup>+</sup> macrophages in primary tumors (PTs) and their spatial relation to tumor-infiltrating B and T cells. Using two breast cancer patient cohorts, we show that CD169<sup>+</sup> macrophages were spatially associated with the presence of B and T cell tertiary lymphoid-like structures (TLLSs) in both PTs and lymph node metastases (LNMs). While co-infiltration of CD169<sup>+</sup>/TLLS in PTs correlated with a worse prognosis, the opposite was found when present in LNMs. RNA sequencing of breast tumors further confirmed that SIGLEC1 (CD169) expression was associated with mature tertiary lymphoid structure (TLS), and T<sub>reg</sub> and B<sub>reg</sub> signatures. We propose that the negative prognostic value related to CD169<sup>+</sup> macrophages in PTs is a consequence of an immunosuppressive tumor environment rich in TLSs, T<sub>regs</sub> and B<sub>regs</sub>.</p>}},
  author       = {{Briem, Oscar and Källberg, Eva and Kimbung, Siker and Veerla, Srinivas and Stenström, Jenny and Hatschek, Thomas and Hagerling, Catharina and Hedenfalk, Ingrid and Leandersson, Karin}},
  issn         = {{2072-6694}},
  keywords     = {{B; breast cancer; CD169; lymph node; macrophage; T; TLS}},
  language     = {{eng}},
  number       = {{4}},
  publisher    = {{MDPI AG}},
  series       = {{Cancers}},
  title        = {{CD169<sup>+</sup> Macrophages in Primary Breast Tumors Associate with Tertiary Lymphoid Structures, T<sub>regs</sub> and a Worse Prognosis for Patients with Advanced Breast Cancer}},
  url          = {{http://dx.doi.org/10.3390/cancers15041262}},
  doi          = {{10.3390/cancers15041262}},
  volume       = {{15}},
  year         = {{2023}},
}