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Fibroblast-Mediated Immunoregulation of Macrophage Function Is Maintained after Irradiation
The abilities of cancer-associated fibroblasts (CAFs) to regulate immune responses in the context of radiotherapy remain largely unknown. This study was undertaken to determine whether ionizing radiation alters the CAF-mediated immunoregulatory effects on macrophages. CAFs were isolated from freshly...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6562631/ https://www.ncbi.nlm.nih.gov/pubmed/31108906 http://dx.doi.org/10.3390/cancers11050689 |
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author | Berzaghi, Rodrigo Ahktar, Muhammad Asad Islam, Ashraful Pedersen, Brede D. Hellevik, Turid Martinez-Zubiaurre, Inigo |
author_facet | Berzaghi, Rodrigo Ahktar, Muhammad Asad Islam, Ashraful Pedersen, Brede D. Hellevik, Turid Martinez-Zubiaurre, Inigo |
author_sort | Berzaghi, Rodrigo |
collection | PubMed |
description | The abilities of cancer-associated fibroblasts (CAFs) to regulate immune responses in the context of radiotherapy remain largely unknown. This study was undertaken to determine whether ionizing radiation alters the CAF-mediated immunoregulatory effects on macrophages. CAFs were isolated from freshly-resected non-small cell lung cancer tumors, while monocyte-derived macrophages were prepared from peripheral blood of healthy donors. Experimental settings included both (CAF-macrophage) co-cultures and incubations of M0 and M1-macrophages in the presence of CAF-conditioned medium (CAF-CM). Functional assays to study macrophage polarization/activation included the expression of cell surface markers, production of nitric oxide, secretion of inflammatory cytokines and migratory capacity. We show that CAFs promote changes in M0-macrophages that harmonize with both M1-and M2-phenotypes. Additionally, CAFs inhibit pro-inflammatory features of M1-macrophages by reducing nitric oxide production, pro-inflammatory cytokines, migration, and M1-surface markers expression. Radiation delivered as single-high dose or in fractioned regimens did not modify the immunoregulatory features exerted by CAFs over macrophages in vitro. Protein expression analyses of CAF supernatants showed that irradiated and non-irradiated CAFs produce approximately the same protein levels of immunoregulators. Thus, CAF-derived soluble factors mediate measurable changes on uncommitted macrophages and down-regulate pro-inflammatory features of M1-polarized macrophages. Notably, ionizing radiation does not curtail the CAF-mediated immunosuppressive effects. |
format | Online Article Text |
id | pubmed-6562631 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-65626312019-06-17 Fibroblast-Mediated Immunoregulation of Macrophage Function Is Maintained after Irradiation Berzaghi, Rodrigo Ahktar, Muhammad Asad Islam, Ashraful Pedersen, Brede D. Hellevik, Turid Martinez-Zubiaurre, Inigo Cancers (Basel) Article The abilities of cancer-associated fibroblasts (CAFs) to regulate immune responses in the context of radiotherapy remain largely unknown. This study was undertaken to determine whether ionizing radiation alters the CAF-mediated immunoregulatory effects on macrophages. CAFs were isolated from freshly-resected non-small cell lung cancer tumors, while monocyte-derived macrophages were prepared from peripheral blood of healthy donors. Experimental settings included both (CAF-macrophage) co-cultures and incubations of M0 and M1-macrophages in the presence of CAF-conditioned medium (CAF-CM). Functional assays to study macrophage polarization/activation included the expression of cell surface markers, production of nitric oxide, secretion of inflammatory cytokines and migratory capacity. We show that CAFs promote changes in M0-macrophages that harmonize with both M1-and M2-phenotypes. Additionally, CAFs inhibit pro-inflammatory features of M1-macrophages by reducing nitric oxide production, pro-inflammatory cytokines, migration, and M1-surface markers expression. Radiation delivered as single-high dose or in fractioned regimens did not modify the immunoregulatory features exerted by CAFs over macrophages in vitro. Protein expression analyses of CAF supernatants showed that irradiated and non-irradiated CAFs produce approximately the same protein levels of immunoregulators. Thus, CAF-derived soluble factors mediate measurable changes on uncommitted macrophages and down-regulate pro-inflammatory features of M1-polarized macrophages. Notably, ionizing radiation does not curtail the CAF-mediated immunosuppressive effects. MDPI 2019-05-17 /pmc/articles/PMC6562631/ /pubmed/31108906 http://dx.doi.org/10.3390/cancers11050689 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Berzaghi, Rodrigo Ahktar, Muhammad Asad Islam, Ashraful Pedersen, Brede D. Hellevik, Turid Martinez-Zubiaurre, Inigo Fibroblast-Mediated Immunoregulation of Macrophage Function Is Maintained after Irradiation |
title | Fibroblast-Mediated Immunoregulation of Macrophage Function Is Maintained after Irradiation |
title_full | Fibroblast-Mediated Immunoregulation of Macrophage Function Is Maintained after Irradiation |
title_fullStr | Fibroblast-Mediated Immunoregulation of Macrophage Function Is Maintained after Irradiation |
title_full_unstemmed | Fibroblast-Mediated Immunoregulation of Macrophage Function Is Maintained after Irradiation |
title_short | Fibroblast-Mediated Immunoregulation of Macrophage Function Is Maintained after Irradiation |
title_sort | fibroblast-mediated immunoregulation of macrophage function is maintained after irradiation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6562631/ https://www.ncbi.nlm.nih.gov/pubmed/31108906 http://dx.doi.org/10.3390/cancers11050689 |
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