Mesenchymal-Stromal Cell-like Melanoma-Associated Fibroblasts Increase IL-10 Production by Macrophages in a Cyclooxygenase/Indoleamine 2,3-Dioxygenase-Dependent Manner.

Autor: Çakır U; Department of Dermatology, Venereology and Dermatooncology, Semmelweis University, 1085 Budapest, Hungary.; Károly Rácz Doctoral School of Clinical Medicine, Semmelweis University, 1085 Budapest, Hungary., Hajdara A; Department of Dermatology, Venereology and Dermatooncology, Semmelweis University, 1085 Budapest, Hungary.; Roska Tamás Doctoral School of Sciences and Technology, Faculty of Information Technology and Bionics, Pázmány Péter Catholic University, 1083 Budapest, Hungary., Széky B; Department of Dermatology, Venereology and Dermatooncology, Semmelweis University, 1085 Budapest, Hungary.; Roska Tamás Doctoral School of Sciences and Technology, Faculty of Information Technology and Bionics, Pázmány Péter Catholic University, 1083 Budapest, Hungary., Mayer B; Department of Dermatology, Venereology and Dermatooncology, Semmelweis University, 1085 Budapest, Hungary., Kárpáti S; Department of Dermatology, Venereology and Dermatooncology, Semmelweis University, 1085 Budapest, Hungary., Mezey É; Adult Stem Cell Section, National Institutes of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA., Silló P; Department of Dermatology, Venereology and Dermatooncology, Semmelweis University, 1085 Budapest, Hungary., Szakács G; Drug Resistance Research Group, Institute of Enzymology, RCNS, Eötvös Lóránd Research Network, 1052 Budapest, Hungary.; Department of Medicine I, Institute of Cancer Research, Comprehensive Cancer Center, Medical University of Vienna, 1090 Vienna, Austria., Füredi A; Drug Resistance Research Group, Institute of Enzymology, RCNS, Eötvös Lóránd Research Network, 1052 Budapest, Hungary., Pós Z; Department of Genetics, Cell and Immunobiology, Semmelweis University, 1085 Budapest, Hungary., Érsek B; Department of Genetics, Cell and Immunobiology, Semmelweis University, 1085 Budapest, Hungary., Sárdy M; Department of Dermatology, Venereology and Dermatooncology, Semmelweis University, 1085 Budapest, Hungary., Németh K; Department of Dermatology, Venereology and Dermatooncology, Semmelweis University, 1085 Budapest, Hungary.
Jazyk: angličtina
Zdroj: Cancers [Cancers (Basel)] 2021 Dec 07; Vol. 13 (24). Date of Electronic Publication: 2021 Dec 07.
DOI: 10.3390/cancers13246173
Abstrakt: Melanoma-associated fibroblasts (MAFs) are integral parts of melanoma, providing a protective network for melanoma cells. The phenotypical and functional similarities between MAFs and mesenchymal stromal cells (MSCs) prompted us to investigate if, similarly to MSCs, MAFs are capable of modulating macrophage functions. Using immunohistochemistry, we showed that MAFs and macrophages are in intimate contact within the tumor stroma. We then demonstrated that MAFs indeed are potent inducers of IL-10 production in various macrophage types in vitro, and this process is greatly augmented by the presence of treatment-naïve and chemotherapy-treated melanoma cells. MAFs derived from thick melanomas appear to be more immunosuppressive than those cultured from thin melanomas. The IL-10 increasing effect is mediated, at least in part, by cyclooxygenase and indoleamine 2,3-dioxygenase. Our data indicate that MAF-induced IL-10 production in macrophages may contribute to melanoma aggressiveness, and targeting the cyclooxygenase and indoleamine 2,3-dioxygenase pathways may abolish MAF-macrophage interactions.
Databáze: MEDLINE
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