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Altered immune signatures in breast cancer lymph nodes with metastases revealed by spatial proteome analyses

Briem, Oscar LU ; Tahin, Balázs ; Frank, Asger Meldgaard LU ; Olsson, Lina M LU ; Sandström Gerdtsson, Anna LU ; Källberg, Eva LU and Leandersson, Karin LU orcid (2025) In Journal of Translational Medicine 23.
Abstract
Background: Metastasis to lymph nodes is strongly associated with reduced survival in breast cancer patients. To increase the understanding on how lymph node metastasis impairs the local immune response in affected lymph
nodes, we here studied spatial proteomic changes of critical lymph node immune populations in uninvolved lymph nodes (UnLN) and paired lymph nodes with metastases (LNM) from five breast cancer patients.

Methods: The proteome was analyzed for cortical lymphocyte compartments, subcapsular sinus (SCS) and medullary sinus (MS) CD169+ macrophages, using the Digital Spatial Profiling (DSP) platform from NanoString.

Results: Our results identified a stable proteome of SCS CD169+ macrophages in LNM, with the... (More)
Background: Metastasis to lymph nodes is strongly associated with reduced survival in breast cancer patients. To increase the understanding on how lymph node metastasis impairs the local immune response in affected lymph
nodes, we here studied spatial proteomic changes of critical lymph node immune populations in uninvolved lymph nodes (UnLN) and paired lymph nodes with metastases (LNM) from five breast cancer patients.

Methods: The proteome was analyzed for cortical lymphocyte compartments, subcapsular sinus (SCS) and medullary sinus (MS) CD169+ macrophages, using the Digital Spatial Profiling (DSP) platform from NanoString.

Results: Our results identified a stable proteome of SCS CD169+ macrophages in LNM, with the exception for downregulation of the anti-apoptotic protein Bcl-xL and FAPα, but a clear reduction in numbers of SCS CD169+ macrophages in LNM. In contrast, the proteome of MS CD169+ macrophages, B-cell compartments and interfollicular T-cells showed altered immune signatures in LNM, indicating that the decline in SCS CD169+ macrophages coincide with a malfunction in the local, anti-tumor immune responses.

Conclusions: The findings from our study support the notion that metastasis to lymph nodes in breast cancer patients modifies local immune responses. These changes may contribute to explain unsuccessful therapeutic responses, and thereby worsened prognosis, for breast cancer patients with LNM. (Less)
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author
; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Breast Cancer, lymph node metastasis, CD169+ macrophages, B-cell follicles, Germinal centers, Interfollicular T-cells
in
Journal of Translational Medicine
volume
23
article number
422 (2025)
pages
14 pages
publisher
BioMed Central (BMC)
ISSN
1479-5876
language
English
LU publication?
yes
id
3a981964-e1ba-4eb1-8451-ebb3e2e9773a
alternative location
https://doi.org/10.1186/s12967-025-06415-4
date added to LUP
2025-04-11 14:12:00
date last changed
2025-04-11 15:49:03
@article{3a981964-e1ba-4eb1-8451-ebb3e2e9773a,
  abstract     = {{Background: Metastasis to lymph nodes is strongly associated with reduced survival in breast cancer patients. To increase the understanding on how lymph node metastasis impairs the local immune response in affected lymph<br/>nodes, we here studied spatial proteomic changes of critical lymph node immune populations in uninvolved lymph nodes (UnLN) and paired lymph nodes with metastases (LNM) from five breast cancer patients.<br/><br/>Methods: The proteome was analyzed for cortical lymphocyte compartments, subcapsular sinus (SCS) and medullary sinus (MS) CD169+ macrophages, using the Digital Spatial Profiling (DSP) platform from NanoString.<br/><br/>Results: Our results identified a stable proteome of SCS CD169+ macrophages in LNM, with the exception for downregulation of the anti-apoptotic protein Bcl-xL and FAPα, but a clear reduction in numbers of SCS CD169+ macrophages in LNM. In contrast, the proteome of MS CD169+ macrophages, B-cell compartments and interfollicular T-cells showed altered immune signatures in LNM, indicating that the decline in SCS CD169+ macrophages coincide with a malfunction in the local, anti-tumor immune responses.<br/><br/>Conclusions: The findings from our study support the notion that metastasis to lymph nodes in breast cancer patients modifies local immune responses. These changes may contribute to explain unsuccessful therapeutic responses, and thereby worsened prognosis, for breast cancer patients with LNM.}},
  author       = {{Briem, Oscar and Tahin, Balázs and Frank, Asger Meldgaard and Olsson, Lina M and Sandström Gerdtsson, Anna and Källberg, Eva and Leandersson, Karin}},
  issn         = {{1479-5876}},
  keywords     = {{Breast Cancer; lymph node metastasis; CD169+ macrophages; B-cell follicles; Germinal centers; Interfollicular T-cells}},
  language     = {{eng}},
  publisher    = {{BioMed Central (BMC)}},
  series       = {{Journal of Translational Medicine}},
  title        = {{Altered immune signatures in breast cancer lymph nodes with metastases revealed by spatial proteome analyses}},
  url          = {{https://doi.org/10.1186/s12967-025-06415-4}},
  volume       = {{23}},
  year         = {{2025}},
}