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Selenite induces po...
Selenite induces posttranscriptional blockade of HLA-E expression and sensitizes tumor cells to CD94/NKG2A-positive NK cells
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- Enqvist, M (författare)
- Karolinska Institutet
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- Nilsonne, G (författare)
- Karolinska Institutet
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Hammarfjord, O (författare)
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- Wallin, RPA (författare)
- Karolinska Institutet
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- Bjorkstrom, NK (författare)
- Karolinska Institutet
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- Bjornstedt, M (författare)
- Karolinska Institutet
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- Hjerpe, A (författare)
- Karolinska Institutet
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- Ljunggren, HG (författare)
- Karolinska Institutet
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- Dobra, K (författare)
- Karolinska Institutet
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- Malmberg, KJ (författare)
- Karolinska Institutet
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- Carlsten, M (författare)
- Karolinska Institutet
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(creator_code:org_t)
- 2011-10-01
- 2011
- Engelska.
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Ingår i: Journal of immunology (Baltimore, Md. : 1950). - : The American Association of Immunologists. - 1550-6606 .- 0022-1767. ; 187:7, s. 3546-3554
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https://doi.org/10.4...
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Abstract
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- 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 (SeO32−), 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.
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Enqvist, M
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Nilsonne, G
-
Hammarfjord, O
-
Wallin, RPA
-
Bjorkstrom, NK
-
Bjornstedt, M
-
visa fler...
-
Hjerpe, A
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Ljunggren, HG
-
Dobra, K
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Malmberg, KJ
-
Carlsten, M
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visa färre...
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Journal of immun ...
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Karolinska Institutet