NDLI: Arsenic trioxide exerts antitumor activity through regulatory T cell depletion mediated by oxidative stress in a murine model of colon cancer.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Lemare, François Annereau, Maxime Nicco, Carole Dauphin, Alain Mongaret, Céline Weill, Bernard Batteux, Frédéric Chéreau, Christiane Alexandre, Jérôme Thomas-Schoemann, Audrey Goldwasser, François
Description	Country affiliation: France Author Affiliation: Thomas-Schoemann A ( Université Paris Descartes, Sorbonne Paris Cité, Unité de Formation et de Recherche des Sciences Pharmaceutiques et Biologiques, 75270 Paris Cedex 06, France. schoemann.audrey@gmail.com)
Abstract	Immunotherapy is a promising antitumor strategy that can successfully be combined with current anticancer treatment. In this study, arsenic trioxide (As(2)O(3)) was shown to increase the antitumor immune response in CT26 colon tumor-bearing mice through the modulation of regulatory T cell (T(reg)) numbers. As(2)O(3) induced T(reg)-selective depletion in vitro. In vivo, tumor-bearing mice injected with 1 mg/kg As(2)O(3) showed a significant decrease in the T(reg)/CD4 cell ratio and in absolute T(reg) count versus controls. As(2)O(3) exerted antitumor effects only in immunocompetent mice and enhanced adoptive immunotherapy effects. Inhibition of As(2)O(3)-induced T(reg) depletion by the NO synthase inhibitor N(G)-nitro-l-arginine methyl ester and the superoxide dismutase mimic manganese [III] tetrakis-(5, 10, 15, 20)-benzoic acid porphyrin suggested that it was mediated by oxidative and nitrosative stress. The differential effect of As(2)O(3) on T(reg) versus other CD4 cells may be related to differences in the cells' redox status, as indicated by significant differences in 2'7'dichlorodihydrofluorescein diacetate and 4,5-diaminofluorescein diacetate fluorescence levels. In conclusion, these results show for the first time, to our knowledge, that low doses As(2)O(3) can delay solid tumor growth by depleting T(regs) through oxidative and nitrosative bursts, and suggest that As(2)O(3) could be used to enhance the antitumor activity of adoptive immunotherapy strategies in human cancer.
ISSN	00221767
e-ISSN	15506606
Journal	The Journal of Immunology
Issue Number	11
Volume Number	189
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2012-12-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Arsenicals Pharmacology Colonic Neoplasms Drug Therapy Immunotherapy, Adoptive Neoplasms, Experimental Oxidative Stress Immunology Oxides T-lymphocytes, Regulatory Drug Effects Animals Cd8-positive T-lymphocytes Transplantation Pathology Enzyme Inhibitors Fluorescein Fluoresceins Lymphocyte Activation Lymphocyte Depletion Metalloporphyrins Mice Mice, Inbred C57bl Ng-nitroarginine Methyl Ester Nitric Oxide Synthase Antagonists & Inhibitors Metabolism Reactive Nitrogen Species Reactive Oxygen Species Superoxide Dismutase Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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