Intra-patient spatial comparison of non-metastatic and metastatic lymph nodes reveals a reduction in CD169+ macrophages within metastatic breast cancers - Research findings

Sep 21, 2026

Uploaded by Theodore

Breast cancer cells suppress host immunity to invade lymph nodes, yet the mechanism remains unclear. Samples from six lymph-node metastatic breast cancer patients were analyzed using bulk transcriptomics, spatial transcriptomics, and imaging mass cytometry, with histological validation across a larger cohort. Paired comparisons showed that CD169+ lymph node sinus macrophages were markedly reduced in metastatic nodes, while other immune cell types were unchanged. CD169+ macrophage infiltration into tumors varied by section and correlated with cancer staging.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages15

Reading Time38 min

AccessFree to download

Summary

Background

Methods

Findings

Interpretation

Research in context

Evidence before this study

Added value of this study

Implications of all the available evidence

Articles Intra-patient spatial comparison of non-metastatic and metastatic lymph nodes reveals a reduction in CD169+ macrophages within metastatic breast cancers Yurina Maeshima,a,b Tatsuki R. Kataoka,c Alexis Vandenbon,d,e Masahiro Hirata,f Yasuhide Takeuchi,f Yutaka Suzuki,g Yukiko Fukui,a Masahiro Kawashima,a Masahiro Takada,a Yumiko Ibi,h Hironori Haga,f Satoshi Morita,h Masakazu Toi,a,i Shinpei Kawaoka,b,j,∗∗ and Kosuke Kawaguchia,k,∗ aDepartment of Breast Surgery, Kyoto University Hospital, Graduate School of Medicine, Shogoin Sakyo-ku, Kyoto 606-8507, Japan bInter-Organ Communication Research Team, Institute for Frontier Life and Medical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan cDepartment of Pathology, Iwate Medical University, Yahaba-cho, Shiwa-gun, Iwate Prefecture 028-3694, Japan dLaboratory of Tissue Homeostasis, Institute for Life and Medical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan eInstitute for Liberal Arts and Sciences, Kyoto University, Kyoto 606-8507, Japan fDepartment of Diagnostic Pathology, Kyoto University, Shogoin Sakyo-ku, Kyoto 606-8507, Japan gGraduate School of Frontier Science, The University of Tokyo, Chiba 277-8562, Japan hDepartment of Biomedical Statistics and Bioinformatics, Kyoto University Graduate School of Medicine, Shogoin Sakyo-ku, Kyoto 606-8507, Japan iTokyo Metropolitan Cancer and Infectious Disease Center, Komagome Hospital, Honkomagome, Bunkyo-ku, Tokyo 113-8677, Japan jDepartment of Integrative Bioanalytics, Institute of Development, Aging and Cancer, Tohoku University, Sendai 980-8575, Japan kDepartment of Breast Surgery, Breast Center, Mie University, Mie 514-0102, Japan Summary Background Breast cancer cells suppress the host immune system to efﬁciently invade the lymph nodes; however, the underlying mechanism remains incompletely understood. Here, we aimed to comprehensively characterise the effects of breast cancers on immune cells in the lymph nodes. Methods We collected non-metastatic and metastatic lymph node samples from 6 patients with breast cancer with lymph node metastasis. We performed bulk transcriptomics, spatial transcriptomics, and imaging mass cytometry to analyse the obtained lymph nodes. Furthermore, we conducted histological analyses against a larger patient cohort (474 slices from 58 patients) . Findings The comparison between paired lymph nodes with and without metastasis from the same patients demonstrated that the number of CD169+ lymph node sinus macrophages, an initiator of anti-cancer immunity, was reduced in metastatic lymph nodes (36 .7 ± 21 .1 vs 7 .3 ± 7 .0 cells/mm2, p = 0 .0087), whereas the numbers of other major immune cell types were unaltered. We also detected that the inﬁltration of CD169+ macrophages into metastasised cancer tissues differed by section location within tumours, suggesting that CD169+ macrophages were gradually decreased after anti-cancer reactions. Furthermore, CD169+ macrophage elimination was prevalent in major breast cancer subtypes and correlated with breast cancer staging (p = 0.022) . Interpretation We concluded that lymph nodes with breast cancer metastases have fewer CD169+ macrophages, which may be detrimental to the activity of anti-cancer immunity. Funding JSPS KAKENHI (16H06279, 20H03451, 20H04842, 22H04925, 19K16770, and 21K15530, 24K02236), JSPS Fellows (JP22KJ1822), AMED (JP21ck0106698), JST FOREST (JPMJFR2062), Caravel, Co., Ltd, Japan Foundation for Applied Enzymology, and Sumitomo Pharma Co., Ltd. under SKIPS. Copyright © 2024 Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license ([http://](http://)[ ](http://)[creativecommons.org/licenses/by-nc-nd/4.0/](creativecommons.org/licenses/by-nc-nd/4.0/)). *Corresponding author. Department of Breast Surgery, Breast Center, Mie University, Mie 1577, Kurimamachiya-cho, Tsu, Mie 514-8507, Japan. **Corresponding author. Department of Integrative Bioanalytics, Inst

FAQs

What was the main goal of this study?

To comprehensively characterize how breast cancer affects immune cells in lymph nodes, using paired comparisons of non-metastatic versus metastatic nodes from the same patients.

Which immune cell type was found to change in metastatic lymph nodes?

The number of CD169+ lymph node sinus macrophages was reduced in metastatic lymph nodes, while other major immune cell types were unaltered.

How was CD169+ macrophage reduction supported beyond the initial analyses?

Infiltration patterns were assessed with histological analyses across a larger cohort, showing section-location differences and a correlation with breast cancer staging.

Sep 21, 2026

Uploaded by Theodore