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Suppression of the hyaluronic acid pathway induces M1 macrophages polarization via STAT1 in glioblastoma
Immunosuppressive tumor microenvironment is a crucial factor that impedes the success of tumor immunotherapy, and tumor-associated macrophages (TAMs) are essential for the formation of tumor immunosuppressive microenvironment. Hyaluronic acid (HA) is highly important brick for glioblastoma microenvi...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9001679/ https://www.ncbi.nlm.nih.gov/pubmed/35410993 http://dx.doi.org/10.1038/s41420-022-00973-y |
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author | Yan, Tao Wang, Kaikai Li, Jiafeng Hu, Hong Yang, He Cai, Meng Liu, Ruijie Li, Honglei Wang, Ning Shi, Ying Hua, Wei Liu, Huailei |
author_facet | Yan, Tao Wang, Kaikai Li, Jiafeng Hu, Hong Yang, He Cai, Meng Liu, Ruijie Li, Honglei Wang, Ning Shi, Ying Hua, Wei Liu, Huailei |
author_sort | Yan, Tao |
collection | PubMed |
description | Immunosuppressive tumor microenvironment is a crucial factor that impedes the success of tumor immunotherapy, and tumor-associated macrophages (TAMs) are essential for the formation of tumor immunosuppressive microenvironment. Hyaluronic acid (HA) is highly important brick for glioblastoma microenvironment, but whether it contributes to TAM polarization and glioblastoma immunosuppressive microenvironment is less well known. In our study, we observed that disrupting glioblastoma HA synthesis or blocking HA binding to its receptor CD44 on macrophages increased the proportion of M1 macrophages by upregulating SIRPα in macrophages, the underlying mechanism was elevated SIRPα enhanced STAT1 phosphorylation and suppressed STAT3 phosphorylation in macrophages. Subsequently, the induced macrophages could inhibit glioblastoma growth via a feedback effect. In addition, 4-methylumbelliferone (4MU), a cholecystitis drug, can disrupt the CD47/SIRPα axis by disturbing glioblastoma HA synthesis. Collectively, these findings indicated that HA plays a crucial role in macrophages polarization and CD47/SIRPα signaling between glioblastoma cells and macrophages, and suppressing the HA pathway may be a new immunotherapeutic approach for glioblastoma. |
format | Online Article Text |
id | pubmed-9001679 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-90016792022-04-27 Suppression of the hyaluronic acid pathway induces M1 macrophages polarization via STAT1 in glioblastoma Yan, Tao Wang, Kaikai Li, Jiafeng Hu, Hong Yang, He Cai, Meng Liu, Ruijie Li, Honglei Wang, Ning Shi, Ying Hua, Wei Liu, Huailei Cell Death Discov Article Immunosuppressive tumor microenvironment is a crucial factor that impedes the success of tumor immunotherapy, and tumor-associated macrophages (TAMs) are essential for the formation of tumor immunosuppressive microenvironment. Hyaluronic acid (HA) is highly important brick for glioblastoma microenvironment, but whether it contributes to TAM polarization and glioblastoma immunosuppressive microenvironment is less well known. In our study, we observed that disrupting glioblastoma HA synthesis or blocking HA binding to its receptor CD44 on macrophages increased the proportion of M1 macrophages by upregulating SIRPα in macrophages, the underlying mechanism was elevated SIRPα enhanced STAT1 phosphorylation and suppressed STAT3 phosphorylation in macrophages. Subsequently, the induced macrophages could inhibit glioblastoma growth via a feedback effect. In addition, 4-methylumbelliferone (4MU), a cholecystitis drug, can disrupt the CD47/SIRPα axis by disturbing glioblastoma HA synthesis. Collectively, these findings indicated that HA plays a crucial role in macrophages polarization and CD47/SIRPα signaling between glioblastoma cells and macrophages, and suppressing the HA pathway may be a new immunotherapeutic approach for glioblastoma. Nature Publishing Group UK 2022-04-11 /pmc/articles/PMC9001679/ /pubmed/35410993 http://dx.doi.org/10.1038/s41420-022-00973-y Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/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/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Yan, Tao Wang, Kaikai Li, Jiafeng Hu, Hong Yang, He Cai, Meng Liu, Ruijie Li, Honglei Wang, Ning Shi, Ying Hua, Wei Liu, Huailei Suppression of the hyaluronic acid pathway induces M1 macrophages polarization via STAT1 in glioblastoma |
title | Suppression of the hyaluronic acid pathway induces M1 macrophages polarization via STAT1 in glioblastoma |
title_full | Suppression of the hyaluronic acid pathway induces M1 macrophages polarization via STAT1 in glioblastoma |
title_fullStr | Suppression of the hyaluronic acid pathway induces M1 macrophages polarization via STAT1 in glioblastoma |
title_full_unstemmed | Suppression of the hyaluronic acid pathway induces M1 macrophages polarization via STAT1 in glioblastoma |
title_short | Suppression of the hyaluronic acid pathway induces M1 macrophages polarization via STAT1 in glioblastoma |
title_sort | suppression of the hyaluronic acid pathway induces m1 macrophages polarization via stat1 in glioblastoma |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9001679/ https://www.ncbi.nlm.nih.gov/pubmed/35410993 http://dx.doi.org/10.1038/s41420-022-00973-y |
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