Mitoxantrone induces natural killer cell maturation in patients with secondary progressive multiple sclerosis.

Mitoxantrone is one of the few drugs approved for the treatment of progressive multiple sclerosis (MS). However, the prolonged use of this potent immunosuppressive agent is limited by the appearance of severe side effects. Apart from its general cytotoxic effect, the mode of action of mitoxantrone o...

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Autores principales:	Coralie Chanvillard, Jason M Millward, Marta Lozano, Isabell Hamann, Friedemann Paul, Frauke Zipp, Jan Dörr, Carmen Infante-Duarte
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c55664edcf084ee19141d3c0f2cddf6c
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spelling	oai:doaj.org-article:c55664edcf084ee19141d3c0f2cddf6c2021-11-18T07:13:56ZMitoxantrone induces natural killer cell maturation in patients with secondary progressive multiple sclerosis.1932-620310.1371/journal.pone.0039625https://doaj.org/article/c55664edcf084ee19141d3c0f2cddf6c2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22768101/?tool=EBIhttps://doaj.org/toc/1932-6203Mitoxantrone is one of the few drugs approved for the treatment of progressive multiple sclerosis (MS). However, the prolonged use of this potent immunosuppressive agent is limited by the appearance of severe side effects. Apart from its general cytotoxic effect, the mode of action of mitoxantrone on the immune system is poorly understood. Thus, to develop safe therapeutic approaches for patients with progressive MS, it is essential to elucidate how mitoxantrone exerts it benefits. Accordingly, we initiated a prospective single-arm open-label study with 19 secondary progressive MS patients. We investigated long-term effects of mitoxantrone on patient peripheral immune subsets using flow cytometry. While we corroborate that mitoxantrone persistently suppresses B cells in vivo, we show for the first time that treatment led to an enrichment of neutrophils and immunomodulatory CD8(low) T cells. Moreover, sustained mitoxantrone applications promoted not only persistent NK cell enrichment but also NK cell maturation. Importantly, this mitoxantrone-induced NK cell maturation was seen only in patients that showed a clinical response to treatment. Our data emphasize the complex immunomodulatory role of mitoxantrone, which may account for its benefit in MS. In particular, these results highlight the contribution of NK cells to mitoxantrone efficacy in progressive MS.Coralie ChanvillardJason M MillwardMarta LozanoIsabell HamannFriedemann PaulFrauke ZippJan DörrCarmen Infante-DuartePublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 6, p e39625 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Coralie Chanvillard Jason M Millward Marta Lozano Isabell Hamann Friedemann Paul Frauke Zipp Jan Dörr Carmen Infante-Duarte Mitoxantrone induces natural killer cell maturation in patients with secondary progressive multiple sclerosis.
description	Mitoxantrone is one of the few drugs approved for the treatment of progressive multiple sclerosis (MS). However, the prolonged use of this potent immunosuppressive agent is limited by the appearance of severe side effects. Apart from its general cytotoxic effect, the mode of action of mitoxantrone on the immune system is poorly understood. Thus, to develop safe therapeutic approaches for patients with progressive MS, it is essential to elucidate how mitoxantrone exerts it benefits. Accordingly, we initiated a prospective single-arm open-label study with 19 secondary progressive MS patients. We investigated long-term effects of mitoxantrone on patient peripheral immune subsets using flow cytometry. While we corroborate that mitoxantrone persistently suppresses B cells in vivo, we show for the first time that treatment led to an enrichment of neutrophils and immunomodulatory CD8(low) T cells. Moreover, sustained mitoxantrone applications promoted not only persistent NK cell enrichment but also NK cell maturation. Importantly, this mitoxantrone-induced NK cell maturation was seen only in patients that showed a clinical response to treatment. Our data emphasize the complex immunomodulatory role of mitoxantrone, which may account for its benefit in MS. In particular, these results highlight the contribution of NK cells to mitoxantrone efficacy in progressive MS.
format	article
author	Coralie Chanvillard Jason M Millward Marta Lozano Isabell Hamann Friedemann Paul Frauke Zipp Jan Dörr Carmen Infante-Duarte
author_facet	Coralie Chanvillard Jason M Millward Marta Lozano Isabell Hamann Friedemann Paul Frauke Zipp Jan Dörr Carmen Infante-Duarte
author_sort	Coralie Chanvillard
title	Mitoxantrone induces natural killer cell maturation in patients with secondary progressive multiple sclerosis.
title_short	Mitoxantrone induces natural killer cell maturation in patients with secondary progressive multiple sclerosis.
title_full	Mitoxantrone induces natural killer cell maturation in patients with secondary progressive multiple sclerosis.
title_fullStr	Mitoxantrone induces natural killer cell maturation in patients with secondary progressive multiple sclerosis.
title_full_unstemmed	Mitoxantrone induces natural killer cell maturation in patients with secondary progressive multiple sclerosis.
title_sort	mitoxantrone induces natural killer cell maturation in patients with secondary progressive multiple sclerosis.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/c55664edcf084ee19141d3c0f2cddf6c
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Mitoxantrone induces natural killer cell maturation in patients with secondary progressive multiple sclerosis.

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