Gutenberg Open Science: Metabolic and inflammatory reprogramming of macrophages by ONC201 translates in a pro-inflammatory environment even in presence of glioblastoma cells

Please use this identifier to cite or link to this item: http://doi.org/10.25358/openscience-8158

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DC Field	Value	Language
dc.contributor.author	Geiß, Carsten	-
dc.contributor.author	Witzler, Claudius	-
dc.contributor.author	Poschet, Gernot	-
dc.contributor.author	Ruf, Wolfram	-
dc.contributor.author	Régnier-Vigouroux, Anne	-
dc.date.accessioned	2022-11-17T08:44:51Z	-
dc.date.available	2022-11-17T08:44:51Z	-
dc.date.issued	2021	-
dc.identifier.uri	https://openscience.ub.uni-mainz.de/handle/20.500.12030/8173	-
dc.description.abstract	Tumor-associated macrophages facilitate tumor progression and resistance to therapy. Their capacity for metabolic and inflammatory reprogramming represents an attractive therapeutic target. ONC201/TIC10 is an anticancer molecule that antagonizes the dopamine receptor D2 and affects mitochondria integrity in tumor cells. We examined whether ONC201 induces a metabolic and pro-inflammatory switch in primary human monocyte-derived macrophages that reactivates their antitumor activities, thus enhancing the onco-toxicity of ONC201. Contrary to glioblastoma cells, macrophages exhibited a low ratio of dopamine receptors D2/D5 gene expression and were resistant to ONC201 cytotoxicity. Macrophages responded to ONC201 with a severe loss of mitochondria integrity, a switch to glycolytic ATP production, alterations in glutamate transport, and a shift towards a pro-inflammatory profile. Treatment of macrophages–glioblastoma cells co-cultures with ONC201 induced similar alterations in glutamatergic and inflammatory gene expression profiles of macrophages. It induced as well metabolic changes and a pro-inflammatory switch of the co-culture milieu. However, these changes did not translate into increased onco-toxicity. This study provides the first evidence that ONC201 affects macrophage immunometabolism and leads to a pro-inflammatory tumor environment. This speaks in favor of implementing ONC201 in combinatorial therapies and warrants further investigation of the mechanisms of action of ONC201 in macrophages and other immune cells.	en_GB
dc.language.iso	eng	de
dc.rights	CC BY-NC	*
dc.rights.uri	https://creativecommons.org/licenses/by-nc/4.0/	*
dc.subject.ddc	570 Biowissenschaften	de_DE
dc.subject.ddc	570 Life sciences	en_GB
dc.subject.ddc	610 Medizin	de_DE
dc.subject.ddc	610 Medical sciences	en_GB
dc.title	Metabolic and inflammatory reprogramming of macrophages by ONC201 translates in a pro-inflammatory environment even in presence of glioblastoma cells	en_GB
dc.type	Zeitschriftenaufsatz	de
dc.identifier.doi	http://doi.org/10.25358/openscience-8158	-
jgu.type.dinitype	article	en_GB
jgu.type.version	Published version	de
jgu.type.resource	Text	de
jgu.organisation.department	FB 04 Medizin	de
jgu.organisation.department	FB 10 Biologie	de
jgu.organisation.number	2700	-
jgu.organisation.number	7970	-
jgu.organisation.name	Johannes Gutenberg-Universität Mainz	-
jgu.rights.accessrights	openAccess	-
jgu.journal.title	European journal of immunology	de
jgu.journal.volume	51	de
jgu.journal.issue	5	de
jgu.pages.start	1246	de
jgu.pages.end	1261	de
jgu.publisher.year	2021	-
jgu.publisher.name	Wiley-VCH	de
jgu.publisher.place	Weinheim	de
jgu.publisher.issn	1521-4141	de
jgu.organisation.place	Mainz	-
jgu.subject.ddccode	570	de
jgu.subject.ddccode	610	de
jgu.publisher.doi	10.1002/eji.202048957	de
jgu.organisation.ror	https://ror.org/023b0x485	-
Appears in collections:	JGU-Publikationen

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