Intra-patient spatial comparison of non-metastatic and metastatic lymph nodes reveals the reduction of CD169+ macrophages by metastatic breast cancersResearch in context
Yurina Maeshima,
Tatsuki R. Kataoka,
Alexis Vandenbon,
Masahiro Hirata,
Yasuhide Takeuchi,
Yutaka Suzuki,
Yukiko Fukui,
Masahiro Kawashima,
Masahiro Takada,
Yumiko Ibi,
Hironori Haga,
Satoshi Morita,
Masakazu Toi,
Shinpei Kawaoka,
Kosuke Kawaguchi
Affiliations
Yurina Maeshima
Department of Breast Surgery, Kyoto University Hospital, Graduate School of Medicine, Shogoin Sakyo-ku, Kyoto 606-8507, Japan; Inter-Organ Communication Research Team, Institute for Frontier Life and Medical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan
Tatsuki R. Kataoka
Department of Pathology, Iwate Medical University, Yahaba-cho, Shiwa-gun, Iwate Prefecture 028-3694, Japan
Alexis Vandenbon
Laboratory of Tissue Homeostasis, Institute for Life and Medical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan; Institute for Liberal Arts and Sciences, Kyoto University, Kyoto 606-8507, Japan
Masahiro Hirata
Department of Diagnostic Pathology, Kyoto University, Shogoin Sakyo-ku, Kyoto 606-8507, Japan
Yasuhide Takeuchi
Department of Diagnostic Pathology, Kyoto University, Shogoin Sakyo-ku, Kyoto 606-8507, Japan
Yutaka Suzuki
Graduate School of Frontier Science, The University of Tokyo, Chiba 277-8562, Japan
Yukiko Fukui
Department of Breast Surgery, Kyoto University Hospital, Graduate School of Medicine, Shogoin Sakyo-ku, Kyoto 606-8507, Japan
Masahiro Kawashima
Department of Breast Surgery, Kyoto University Hospital, Graduate School of Medicine, Shogoin Sakyo-ku, Kyoto 606-8507, Japan
Masahiro Takada
Department of Breast Surgery, Kyoto University Hospital, Graduate School of Medicine, Shogoin Sakyo-ku, Kyoto 606-8507, Japan
Yumiko Ibi
Department of Biomedical Statistics and Bioinformatics, Kyoto University Graduate School of Medicine, Shogoin Sakyo-ku, Kyoto 606-8507, Japan
Hironori Haga
Department of Diagnostic Pathology, Kyoto University, Shogoin Sakyo-ku, Kyoto 606-8507, Japan
Satoshi Morita
Department of Biomedical Statistics and Bioinformatics, Kyoto University Graduate School of Medicine, Shogoin Sakyo-ku, Kyoto 606-8507, Japan
Masakazu Toi
Department of Breast Surgery, Kyoto University Hospital, Graduate School of Medicine, Shogoin Sakyo-ku, Kyoto 606-8507, Japan; Tokyo Metropolitan Cancer and Infectious Disease Center, Komagome Hospital, Honkomagome, Bunkyo-ku, Tokyo 113-8677, Japan
Shinpei Kawaoka
Inter-Organ Communication Research Team, Institute for Frontier Life and Medical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan; Department of Integrative Bioanalytics, Institute of Development, Aging and Cancer, Tohoku University, Sendai 980-8575, Japan; Corresponding author. Department of Integrative Bioanalytics, Institute of Development, Aging and Cancer (IDAC), Tohoku University, 4-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan.
Kosuke Kawaguchi
Department of Breast Surgery, Kyoto University Hospital, Graduate School of Medicine, Shogoin Sakyo-ku, Kyoto 606-8507, Japan; Department of Breast Surgery, Breast Center, Mie University, Mie 514-0102, Japan; Corresponding author. Department of Breast Surgery, Breast Center, Mie University, Mie 1577, Kurimamachiya-cho, Tsu, Mie 514-8507, 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.
