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Macrophages reprogrammed by lung cancer microparticles promote tumor development via release of IL-1β
Despite their mutual antagonism, inflammation and immunosuppression coexist in tumor microenvironments due to tumor and immune cell interactions, but the underlying mechanism remains unclear. Previously, we showed that tumor cell-derived microparticles induce an M2 phenotype characterized by immunos...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7784894/ https://www.ncbi.nlm.nih.gov/pubmed/31649305 http://dx.doi.org/10.1038/s41423-019-0313-2 |
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author | Chen, Jie Sun, Weiwei Zhang, Huafeng Ma, Jingwei Xu, Pingwei Yu, Yuandong Fang, Haiqing Zhou, Li Lv, Jiadi Xie, Jing Liu, Yuying Tang, Ke Huang, Bo |
author_facet | Chen, Jie Sun, Weiwei Zhang, Huafeng Ma, Jingwei Xu, Pingwei Yu, Yuandong Fang, Haiqing Zhou, Li Lv, Jiadi Xie, Jing Liu, Yuying Tang, Ke Huang, Bo |
author_sort | Chen, Jie |
collection | PubMed |
description | Despite their mutual antagonism, inflammation and immunosuppression coexist in tumor microenvironments due to tumor and immune cell interactions, but the underlying mechanism remains unclear. Previously, we showed that tumor cell-derived microparticles induce an M2 phenotype characterized by immunosuppression in tumor-infiltrating macrophages. Here, we further showed that lung cancer microparticles (L-MPs) induce macrophages to release a key proinflammatory cytokine, IL-1β, thus promoting lung cancer development. The underlying mechanism involves the activation of TLR3 and the NLRP3 inflammasome by L-MPs. More importantly, tyrosine kinase inhibitor treatment-induced L-MPs also induce human macrophages to release IL-1β, leading to a tumor-promoting effect in a humanized mouse model. These findings demonstrated that in addition to their anti-inflammatory effect, L-MPs induce a proinflammatory phenotype in tumor-infiltrating macrophages, promoting the development of inflammatory and immunosuppressive tumor microenvironments. |
format | Online Article Text |
id | pubmed-7784894 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-77848942021-01-14 Macrophages reprogrammed by lung cancer microparticles promote tumor development via release of IL-1β Chen, Jie Sun, Weiwei Zhang, Huafeng Ma, Jingwei Xu, Pingwei Yu, Yuandong Fang, Haiqing Zhou, Li Lv, Jiadi Xie, Jing Liu, Yuying Tang, Ke Huang, Bo Cell Mol Immunol Article Despite their mutual antagonism, inflammation and immunosuppression coexist in tumor microenvironments due to tumor and immune cell interactions, but the underlying mechanism remains unclear. Previously, we showed that tumor cell-derived microparticles induce an M2 phenotype characterized by immunosuppression in tumor-infiltrating macrophages. Here, we further showed that lung cancer microparticles (L-MPs) induce macrophages to release a key proinflammatory cytokine, IL-1β, thus promoting lung cancer development. The underlying mechanism involves the activation of TLR3 and the NLRP3 inflammasome by L-MPs. More importantly, tyrosine kinase inhibitor treatment-induced L-MPs also induce human macrophages to release IL-1β, leading to a tumor-promoting effect in a humanized mouse model. These findings demonstrated that in addition to their anti-inflammatory effect, L-MPs induce a proinflammatory phenotype in tumor-infiltrating macrophages, promoting the development of inflammatory and immunosuppressive tumor microenvironments. Nature Publishing Group UK 2019-10-24 2020-12 /pmc/articles/PMC7784894/ /pubmed/31649305 http://dx.doi.org/10.1038/s41423-019-0313-2 Text en © The Author(s) 2019 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 Chen, Jie Sun, Weiwei Zhang, Huafeng Ma, Jingwei Xu, Pingwei Yu, Yuandong Fang, Haiqing Zhou, Li Lv, Jiadi Xie, Jing Liu, Yuying Tang, Ke Huang, Bo Macrophages reprogrammed by lung cancer microparticles promote tumor development via release of IL-1β |
title | Macrophages reprogrammed by lung cancer microparticles promote tumor development via release of IL-1β |
title_full | Macrophages reprogrammed by lung cancer microparticles promote tumor development via release of IL-1β |
title_fullStr | Macrophages reprogrammed by lung cancer microparticles promote tumor development via release of IL-1β |
title_full_unstemmed | Macrophages reprogrammed by lung cancer microparticles promote tumor development via release of IL-1β |
title_short | Macrophages reprogrammed by lung cancer microparticles promote tumor development via release of IL-1β |
title_sort | macrophages reprogrammed by lung cancer microparticles promote tumor development via release of il-1β |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7784894/ https://www.ncbi.nlm.nih.gov/pubmed/31649305 http://dx.doi.org/10.1038/s41423-019-0313-2 |
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