患者内非转移性和转移性淋巴结的空间比较揭示了转移性乳腺癌中 CD169 巨噬细胞的减少。
Intra-patient spatial comparison of non-metastatic and metastatic lymph nodes reveals a reduction in CD169+ macrophages within metastatic breast cancers.
发表日期:2024 Aug 21
作者:
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
来源:
EBioMedicine
摘要:
乳腺癌细胞抑制宿主免疫系统,有效侵入淋巴结;然而,其根本机制仍不完全清楚。在这里,我们的目的是全面表征乳腺癌对淋巴结免疫细胞的影响。我们收集了 6 名淋巴结转移的乳腺癌患者的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量细胞术来分析获得的淋巴结。此外,我们对更大的患者队列(58 名患者的 474 个切片)进行了组织学分析。对来自同一患者的有转移和无转移的配对淋巴结进行比较表明,CD169 淋巴结窦巨噬细胞(抗癌的启动子)的数量转移性淋巴结中的免疫细胞减少(36.7 ± 21.1 vs 7.3 ± 7.0 cells/mm2,p = 0.0087),而其他主要免疫细胞类型的数量没有变化。我们还检测到,CD169巨噬细胞向转移癌组织的浸润因肿瘤内切片位置的不同而不同,这表明CD169巨噬细胞在抗癌反应后逐渐减少。此外,CD169巨噬细胞消除在主要乳腺癌亚型中普遍存在,并且与乳腺癌分期相关(p = 0.022)。我们得出结论,乳腺癌转移的淋巴结具有较少的CD169巨噬细胞,这可能不利于抗癌免疫活性.JSPS KAKENHI (16H06279、20H03451、20H04842、22H04925、19K16770 和 21K15530、24K02236)、JSPS 研究员 (JP22KJ1822)、AMED (JP21ck0106698)、JST FOREST (JPMJ) FR2062),Caravel,有限公司,日本应用酶学基金会,和 Sumitomo Pharma Co., Ltd. 下的 SKIPS。版权所有 © 2024。由 Elsevier B.V. 出版。
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/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).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.Copyright © 2024. Published by Elsevier B.V.