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Fibroblast-Mediated Immunoregulation of Macrophage Function Is Maintained after Irradiation

Permanent link
https://hdl.handle.net/10037/16378
DOI
https://doi.org/10.3390/cancers11050689
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Date
2019-05-17
Type
Journal article
Tidsskriftartikkel
Peer reviewed

Author
Berzaghi, Rodrigo; Akhtar, Muhammad Asad; Islam, Md Ashraful; Pedersen, Brede Dille; Hellevik, Turid; Martinez, Inigo Zubiavrre
Abstract
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.
Description
Source at https://doi.org/10.3390/cancers11050689.
Publisher
MDPI
Citation
Berzaghi, R., Akhtar, M.A., Islam, A., Pedersen, B.D., Hellevik, T. & Martinez-Zubiaurre, I. (201). Fibroblast-Mediated Immunoregulation of Macrophage Function Is Maintained after Irradiation. Cancers, 11(5), 689. https://doi.org/10.3390/cancers11050689
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