NDLI: Selenite induces posttranscriptional blockade of HLA-E expression and sensitizes tumor cells to CD94/NKG2A-positive NK cells.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Nilsonne, Gustav Hammarfjord, Oscar Ljunggren, Hans-Gustaf Malmberg, Karl-Johan Hjerpe, Anders Enqvist, Monika Björnstedt, Mikael Björkström, Niklas K. Wallin, Robert P. A. Dobra, Katalin Carlsten, Mattias
Description	Country affiliation: Sweden Author Affiliation: Enqvist M ( Department of Medicine, Center for Infectious Medicine, Karolinska Institute, Karolinska University Hospital Huddinge, 141 86 Stockholm, Sweden.)
Abstract	CD94/NKG2A is an inhibitory receptor that controls the activity of a large proportion of human NK cells following interactions with the nonclassical HLA class Ib molecule HLA-E expressed on target cells. In this study, we show that selenite (SeO(3)(2-)), an inorganic selenium compound, induces an almost complete loss of cell surface expression of HLA-E on tumor cells of various origins. Selenite abrogated the HLA-E expression at a posttranscriptional level, since selenite exposure led to a dose-dependent decrease in cellular HLA-E protein expression whereas the mRNA levels remained intact. The loss of HLA-E expression following selenite treatment was associated with decreased levels of intracellular free thiols in the tumor cells, suggesting that the reduced HLA-E protein synthesis was caused by oxidative stress. Indeed, HLA-E expression and the level of free thiols remained intact following treatment with selenomethionine, a selenium compound that does not generate oxidative stress. Loss of HLA-E expression, but not of total HLA class I expression, on tumor cells resulted in increased susceptibility to CD94/NK group 2A-positive NK cells. Our results suggest that selenite may be used to potentiate the anti-tumor cytotoxicity in settings of NK cell-based immunotherapies.
ISSN	00221767
e-ISSN	15506606
Journal	The Journal of Immunology
Issue Number	7
Volume Number	187
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2011-10-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Antineoplastic Agents Pharmacology Histocompatibility Antigens Class I Biosynthesis Killer Cells, Natural Immunology Sodium Selenite Blotting, Western Cell Line, Tumor Cell Separation Cytotoxicity, Immunologic Flow Cytometry Nk Cell Lectin-like Receptor Subfamily C Metabolism Nk Cell Lectin-like Receptor Subfamily D Oxidative Stress Rna Interference Reverse Transcriptase Polymerase Chain Reaction Research Support, Non-u.s. Gov't Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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