4-methylumbelliferone-mediated polarization of M1 macrophages correlate with decreased hepatocellular carcinoma aggressiveness in mice

Abstract Hepatocellular carcinoma (HCC) arises in the setting of advanced liver fibrosis, a dynamic and complex inflammatory disease. The tumor microenvironment (TME) is a mixture of cellular components including cancer cells, cancer stem cells (CSCs), tumor-associated macrophages (TAM), and dendrit...

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Autores principales:	Marcelo M. Rodríguez, Agostina Onorato, María José Cantero, Luciana Domínguez, Juan Bayo, Esteban Fiore, Mariana García, Catalina Atorrasagasti, Ali Canbay, Mariana Malvicini, Guillermo D. Mazzolini
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3d3c6f33ea01415b96af9f1753a19b1c
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spelling	oai:doaj.org-article:3d3c6f33ea01415b96af9f1753a19b1c2021-12-02T11:39:27Z4-methylumbelliferone-mediated polarization of M1 macrophages correlate with decreased hepatocellular carcinoma aggressiveness in mice10.1038/s41598-021-85491-02045-2322https://doaj.org/article/3d3c6f33ea01415b96af9f1753a19b1c2021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-85491-0https://doaj.org/toc/2045-2322Abstract Hepatocellular carcinoma (HCC) arises in the setting of advanced liver fibrosis, a dynamic and complex inflammatory disease. The tumor microenvironment (TME) is a mixture of cellular components including cancer cells, cancer stem cells (CSCs), tumor-associated macrophages (TAM), and dendritic cells (DCs), which might drive to tumor progression and resistance to therapies. In this work, we study the effects of 4-methylumbelliferone (4Mu) on TME and how this change could be exploited to promote a potent immune response against HCC. First, we observed that 4Mu therapy induced a switch of hepatic macrophages (Mϕ) towards an M1 type profile, and HCC cells (Hepa129 cells) exposed to conditioned medium (CM) derived from Mϕ treated with 4Mu showed reduced expression of several CSCs markers and aggressiveness. HCC cells incubated with CM derived from Mϕ treated with 4Mu grew in immunosuppressed mice while presented delayed tumor progression in immunocompetent mice. HCC cells treated with 4Mu were more susceptible to phagocytosis by DCs, and when DCs were pulsed with HCC cells previously treated with 4Mu displayed a potent antitumoral effect in therapeutic vaccination protocols. In conclusion, 4Mu has the ability to modulate TME into a less hostile milieu and to potentiate immunotherapeutic strategies against HCC.Marcelo M. RodríguezAgostina OnoratoMaría José CanteroLuciana DomínguezJuan BayoEsteban FioreMariana GarcíaCatalina AtorrasagastiAli CanbayMariana MalviciniGuillermo D. MazzoliniNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Marcelo M. Rodríguez Agostina Onorato María José Cantero Luciana Domínguez Juan Bayo Esteban Fiore Mariana García Catalina Atorrasagasti Ali Canbay Mariana Malvicini Guillermo D. Mazzolini 4-methylumbelliferone-mediated polarization of M1 macrophages correlate with decreased hepatocellular carcinoma aggressiveness in mice
description	Abstract Hepatocellular carcinoma (HCC) arises in the setting of advanced liver fibrosis, a dynamic and complex inflammatory disease. The tumor microenvironment (TME) is a mixture of cellular components including cancer cells, cancer stem cells (CSCs), tumor-associated macrophages (TAM), and dendritic cells (DCs), which might drive to tumor progression and resistance to therapies. In this work, we study the effects of 4-methylumbelliferone (4Mu) on TME and how this change could be exploited to promote a potent immune response against HCC. First, we observed that 4Mu therapy induced a switch of hepatic macrophages (Mϕ) towards an M1 type profile, and HCC cells (Hepa129 cells) exposed to conditioned medium (CM) derived from Mϕ treated with 4Mu showed reduced expression of several CSCs markers and aggressiveness. HCC cells incubated with CM derived from Mϕ treated with 4Mu grew in immunosuppressed mice while presented delayed tumor progression in immunocompetent mice. HCC cells treated with 4Mu were more susceptible to phagocytosis by DCs, and when DCs were pulsed with HCC cells previously treated with 4Mu displayed a potent antitumoral effect in therapeutic vaccination protocols. In conclusion, 4Mu has the ability to modulate TME into a less hostile milieu and to potentiate immunotherapeutic strategies against HCC.
format	article
author	Marcelo M. Rodríguez Agostina Onorato María José Cantero Luciana Domínguez Juan Bayo Esteban Fiore Mariana García Catalina Atorrasagasti Ali Canbay Mariana Malvicini Guillermo D. Mazzolini
author_facet	Marcelo M. Rodríguez Agostina Onorato María José Cantero Luciana Domínguez Juan Bayo Esteban Fiore Mariana García Catalina Atorrasagasti Ali Canbay Mariana Malvicini Guillermo D. Mazzolini
author_sort	Marcelo M. Rodríguez
title	4-methylumbelliferone-mediated polarization of M1 macrophages correlate with decreased hepatocellular carcinoma aggressiveness in mice
title_short	4-methylumbelliferone-mediated polarization of M1 macrophages correlate with decreased hepatocellular carcinoma aggressiveness in mice
title_full	4-methylumbelliferone-mediated polarization of M1 macrophages correlate with decreased hepatocellular carcinoma aggressiveness in mice
title_fullStr	4-methylumbelliferone-mediated polarization of M1 macrophages correlate with decreased hepatocellular carcinoma aggressiveness in mice
title_full_unstemmed	4-methylumbelliferone-mediated polarization of M1 macrophages correlate with decreased hepatocellular carcinoma aggressiveness in mice
title_sort	4-methylumbelliferone-mediated polarization of m1 macrophages correlate with decreased hepatocellular carcinoma aggressiveness in mice
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/3d3c6f33ea01415b96af9f1753a19b1c
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4-methylumbelliferone-mediated polarization of M1 macrophages correlate with decreased hepatocellular carcinoma aggressiveness in mice

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