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.
Department of Pathology, Iwate Medical University, Yahaba-cho, Shiwa-gun, Iwate Prefecture 028-3694, Japan.
EBioMedicine. 2024 Sep;107:105271. doi: 10.1016/j.ebiom.2024.105271. Epub 2024 Aug 21.
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.
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).
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/mm, 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).
We concluded that lymph nodes with breast cancer metastases have fewer CD169 macrophages, which may be detrimental to the activity of anti-cancer immunity.
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.
乳腺癌细胞抑制宿主免疫系统，从而有效地侵袭淋巴结；然而，其潜在机制尚不完全清楚。在这里，我们旨在全面描述乳腺癌对淋巴结中免疫细胞的影响。
我们从 6 名患有淋巴结转移的乳腺癌患者中收集了非转移性和转移性淋巴结样本。我们进行了批量转录组学、空间转录组学和成像质谱细胞术分析，以研究获得的淋巴结。此外，我们针对更大的患者队列（58 名患者的 474 个切片）进行了组织学分析。
同一患者伴有和不伴有转移的配对淋巴结之间的比较表明，淋巴结窦巨噬细胞（CD169）的数量减少，而淋巴结窦巨噬细胞是抗癌免疫的启动者，在转移性淋巴结中（36.7 ± 21.1 与 7.3 ± 7.0 个细胞/mm，p = 0.0087），而其他主要免疫细胞类型的数量没有改变。我们还发现，CD169 巨噬细胞浸润转移癌组织的位置在肿瘤内不同，表明 CD169 巨噬细胞在抗癌反应后逐渐减少。此外，CD169 巨噬细胞的消除在主要乳腺癌亚型中很常见，并且与乳腺癌分期相关（p = 0.022）。
带有乳腺癌转移的淋巴结中 CD169 巨噬细胞较少，这可能不利于抗癌免疫的活性。
JSPS KAKENHI（16H06279、20H03451、20H04842、22H04925、19K16770 和 21K15530、24K02236）、JSPS 研究员（JP22KJ1822）、AMED（JP21ck0106698）、JST FOREST（JPMJFR2062）、Caravel 有限公司、日本应用酶学基金会和住友制药株式会社根据 SKIPS。
