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

## TL;DR

This study shows how breast cancer metastasis to lymph nodes disrupts local immune responses, potentially explaining worse patient outcomes.

## Contribution

The study reveals specific immune proteomic changes in lymph node metastases using spatial profiling.

## Key findings

- SCS CD169+ macrophages in LNM show reduced numbers and downregulation of Bcl-xL and FAPα.
- MS CD169+ macrophages, B-cells, and T-cells in LNM display altered immune signatures.
- Metastasis to lymph nodes modifies local immune responses, possibly leading to poor prognosis.

## Abstract

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.

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.

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.

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.

The online version contains supplementary material available at 10.1186/s12967-025-06415-4.