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
影响因子:
4.6
通讯作者:
Pflanz S
中科院分区:
文献类型:
--
作者:
Durlanik S;Fundel-Clemens K;Viollet C;Huber HJ;Lenter M;Kitt K;Pflanz S
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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