CD276 is an important player in macrophage recruitment into the tumor and an upstream regulator for PAI-1
Abstract 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 bee...
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Nature Portfolio
2021
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oai:doaj.org-article:3514e95bf4724fdea484cf4f1f37996c2021-12-02T17:57:16ZCD276 is an important player in macrophage recruitment into the tumor and an upstream regulator for PAI-110.1038/s41598-021-94360-92045-2322https://doaj.org/article/3514e95bf4724fdea484cf4f1f37996c2021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-94360-9https://doaj.org/toc/2045-2322Abstract 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.Sibel DurlanikKatrin Fundel-ClemensCoralie ViolletHeinrich J. HuberMartin LenterKerstin KittStefan PflanzNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021) |
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Medicine R Science Q Sibel Durlanik Katrin Fundel-Clemens Coralie Viollet Heinrich J. Huber Martin Lenter Kerstin Kitt Stefan Pflanz CD276 is an important player in macrophage recruitment into the tumor and an upstream regulator for PAI-1 |
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Abstract 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. |
format |
article |
author |
Sibel Durlanik Katrin Fundel-Clemens Coralie Viollet Heinrich J. Huber Martin Lenter Kerstin Kitt Stefan Pflanz |
author_facet |
Sibel Durlanik Katrin Fundel-Clemens Coralie Viollet Heinrich J. Huber Martin Lenter Kerstin Kitt Stefan Pflanz |
author_sort |
Sibel Durlanik |
title |
CD276 is an important player in macrophage recruitment into the tumor and an upstream regulator for PAI-1 |
title_short |
CD276 is an important player in macrophage recruitment into the tumor and an upstream regulator for PAI-1 |
title_full |
CD276 is an important player in macrophage recruitment into the tumor and an upstream regulator for PAI-1 |
title_fullStr |
CD276 is an important player in macrophage recruitment into the tumor and an upstream regulator for PAI-1 |
title_full_unstemmed |
CD276 is an important player in macrophage recruitment into the tumor and an upstream regulator for PAI-1 |
title_sort |
cd276 is an important player in macrophage recruitment into the tumor and an upstream regulator for pai-1 |
publisher |
Nature Portfolio |
publishDate |
2021 |
url |
https://doaj.org/article/3514e95bf4724fdea484cf4f1f37996c |
work_keys_str_mv |
AT sibeldurlanik cd276isanimportantplayerinmacrophagerecruitmentintothetumorandanupstreamregulatorforpai1 AT katrinfundelclemens cd276isanimportantplayerinmacrophagerecruitmentintothetumorandanupstreamregulatorforpai1 AT coralieviollet cd276isanimportantplayerinmacrophagerecruitmentintothetumorandanupstreamregulatorforpai1 AT heinrichjhuber cd276isanimportantplayerinmacrophagerecruitmentintothetumorandanupstreamregulatorforpai1 AT martinlenter cd276isanimportantplayerinmacrophagerecruitmentintothetumorandanupstreamregulatorforpai1 AT kerstinkitt cd276isanimportantplayerinmacrophagerecruitmentintothetumorandanupstreamregulatorforpai1 AT stefanpflanz cd276isanimportantplayerinmacrophagerecruitmentintothetumorandanupstreamregulatorforpai1 |
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1718379037981671424 |