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Hypoxia inducible factor HIF-1 promotes myeloid-derived suppressor cells accumulation through ENTPD2/CD39L1 in hepatocellular carcinoma
Myeloid-derived suppressor cells (MDSCs) possess immunosuppressive activities, which allow cancers to escape immune surveillance and become non-responsive to immune checkpoints blockade. Here we report hypoxia as a cause of MDSC accumulation. Using hepatocellular carcinoma (HCC) as a cancer model, w...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5593860/ https://www.ncbi.nlm.nih.gov/pubmed/28894087 http://dx.doi.org/10.1038/s41467-017-00530-7 |
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author | Chiu, David Kung-Chun Tse, Aki Pui-Wah Xu, Iris Ming-Jing Di Cui, Jane Lai, Robin Kit-Ho Li, Lynna Lan Koh, Hui-Yu Tsang, Felice Ho-Ching Wei, Larry Lai Wong, Chun-Ming Ng, Irene Oi-Lin Wong, Carmen Chak-Lui |
author_facet | Chiu, David Kung-Chun Tse, Aki Pui-Wah Xu, Iris Ming-Jing Di Cui, Jane Lai, Robin Kit-Ho Li, Lynna Lan Koh, Hui-Yu Tsang, Felice Ho-Ching Wei, Larry Lai Wong, Chun-Ming Ng, Irene Oi-Lin Wong, Carmen Chak-Lui |
author_sort | Chiu, David Kung-Chun |
collection | PubMed |
description | Myeloid-derived suppressor cells (MDSCs) possess immunosuppressive activities, which allow cancers to escape immune surveillance and become non-responsive to immune checkpoints blockade. Here we report hypoxia as a cause of MDSC accumulation. Using hepatocellular carcinoma (HCC) as a cancer model, we show that hypoxia, through stabilization of hypoxia-inducible factor-1 (HIF-1), induces ectoenzyme, ectonucleoside triphosphate diphosphohydrolase 2 (ENTPD2/CD39L1), in cancer cells, causing its overexpression in HCC clinical specimens. Overexpression of ENTPD2 is found as a poor prognostic indicator for HCC. Mechanistically, we demonstrate that ENTPD2 converts extracellular ATP to 5′-AMP, which prevents the differentiation of MDSCs and therefore promotes the maintenance of MDSCs. We further find that ENTPD2 inhibition is able to mitigate cancer growth and enhance the efficiency and efficacy of immune checkpoint inhibitors. Our data suggest that ENTPD2 may be a good prognostic marker and therapeutic target for cancer patients, especially those receiving immune therapy. |
format | Online Article Text |
id | pubmed-5593860 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-55938602017-09-13 Hypoxia inducible factor HIF-1 promotes myeloid-derived suppressor cells accumulation through ENTPD2/CD39L1 in hepatocellular carcinoma Chiu, David Kung-Chun Tse, Aki Pui-Wah Xu, Iris Ming-Jing Di Cui, Jane Lai, Robin Kit-Ho Li, Lynna Lan Koh, Hui-Yu Tsang, Felice Ho-Ching Wei, Larry Lai Wong, Chun-Ming Ng, Irene Oi-Lin Wong, Carmen Chak-Lui Nat Commun Article Myeloid-derived suppressor cells (MDSCs) possess immunosuppressive activities, which allow cancers to escape immune surveillance and become non-responsive to immune checkpoints blockade. Here we report hypoxia as a cause of MDSC accumulation. Using hepatocellular carcinoma (HCC) as a cancer model, we show that hypoxia, through stabilization of hypoxia-inducible factor-1 (HIF-1), induces ectoenzyme, ectonucleoside triphosphate diphosphohydrolase 2 (ENTPD2/CD39L1), in cancer cells, causing its overexpression in HCC clinical specimens. Overexpression of ENTPD2 is found as a poor prognostic indicator for HCC. Mechanistically, we demonstrate that ENTPD2 converts extracellular ATP to 5′-AMP, which prevents the differentiation of MDSCs and therefore promotes the maintenance of MDSCs. We further find that ENTPD2 inhibition is able to mitigate cancer growth and enhance the efficiency and efficacy of immune checkpoint inhibitors. Our data suggest that ENTPD2 may be a good prognostic marker and therapeutic target for cancer patients, especially those receiving immune therapy. Nature Publishing Group UK 2017-09-11 /pmc/articles/PMC5593860/ /pubmed/28894087 http://dx.doi.org/10.1038/s41467-017-00530-7 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Chiu, David Kung-Chun Tse, Aki Pui-Wah Xu, Iris Ming-Jing Di Cui, Jane Lai, Robin Kit-Ho Li, Lynna Lan Koh, Hui-Yu Tsang, Felice Ho-Ching Wei, Larry Lai Wong, Chun-Ming Ng, Irene Oi-Lin Wong, Carmen Chak-Lui Hypoxia inducible factor HIF-1 promotes myeloid-derived suppressor cells accumulation through ENTPD2/CD39L1 in hepatocellular carcinoma |
title | Hypoxia inducible factor HIF-1 promotes myeloid-derived suppressor cells accumulation through ENTPD2/CD39L1 in hepatocellular carcinoma |
title_full | Hypoxia inducible factor HIF-1 promotes myeloid-derived suppressor cells accumulation through ENTPD2/CD39L1 in hepatocellular carcinoma |
title_fullStr | Hypoxia inducible factor HIF-1 promotes myeloid-derived suppressor cells accumulation through ENTPD2/CD39L1 in hepatocellular carcinoma |
title_full_unstemmed | Hypoxia inducible factor HIF-1 promotes myeloid-derived suppressor cells accumulation through ENTPD2/CD39L1 in hepatocellular carcinoma |
title_short | Hypoxia inducible factor HIF-1 promotes myeloid-derived suppressor cells accumulation through ENTPD2/CD39L1 in hepatocellular carcinoma |
title_sort | hypoxia inducible factor hif-1 promotes myeloid-derived suppressor cells accumulation through entpd2/cd39l1 in hepatocellular carcinoma |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5593860/ https://www.ncbi.nlm.nih.gov/pubmed/28894087 http://dx.doi.org/10.1038/s41467-017-00530-7 |
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