CD276 is an important player in macrophage recruitment into the tumor and an upstream regulator for PAI-1.

CD276 is an important player in macrophage recruitment into the tumor and an upstream regulator for PAI-1.
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DOI:
10.1038/s41598-021-94360-9
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发表时间:
2021-07-21
期刊:
影响因子:
4.6
通讯作者:
Pflanz S
Pflanz S
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Durlanik S;Fundel-Clemens K;Viollet C;Huber HJ;Lenter M;Kitt K;Pflanz S

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超过70%的结直肠癌、前列腺癌、卵巢癌、胰腺癌和乳腺癌标本显示CD 276(B7-H3)表达,这是一种潜在的免疫检查点家族成员。一些研究表明,癌细胞中的高CD 276表达与不良临床预后相关。这与较低的肿瘤浸润白细胞的存在有关。其中,肿瘤相关巨噬细胞可占肿瘤质量的50%,并被认为通过各种机制支持肿瘤生长。然而,缺乏关于CD 276功能和相互作用伴侣的信息阻碍了对CD 276作为肿瘤学治疗靶点的严格评价。因此,我们的目的是通过采用具有人细胞的3D球体共培养系统来理解CD 276在肿瘤-巨噬细胞相互作用中的相关性。我们的数据显示了肿瘤表达的CD 276对巨噬细胞募集到肿瘤球体中的作用,以及对细胞外基质调节剂派-1的调节。此外,我们专注于巨噬细胞表达的CD 276的实验表明,抗体依赖性CD 276接合触发人巨噬细胞中的主要抑制性信号传导网络。
More than 70% of colorectal, prostate, ovarian, pancreatic and breast cancer specimens show expression of CD276 (B7–H3), a potential immune checkpoint family member. Several studies have shown that high CD276 expression in cancer cells correlates with a poor clinical prognosis. This has been associated with the presence of lower tumor infiltrating leukocytes. Among those, tumor-associated macrophages can comprise up to 50% of the tumor mass and are thought to support tumor growth through various mechanisms. However, a lack of information on CD276 function and interaction partner(s) impedes rigorous evaluation of CD276 as a therapeutic target in oncology. Therefore, we aimed to understand the relevance of CD276 in tumor-macrophage interaction by employing a 3D spheroid coculture system with human cells. Our data show a role for tumor-expressed CD276 on the macrophage recruitment into the tumor spheroid, and also in regulation of the extracellular matrix modulator PAI-1. Furthermore, our experiments focusing on macrophage-expressed CD276 suggest that the antibody-dependent CD276 engagement triggers predominantly inhibitory signaling networks in human macrophages.
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