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Distinct human circulating NKp30+FcεRIγ+CD8+ T cell population exhibiting high natural killer-like antitumor potential

CD8+ T cells are considered prototypical cells of adaptive immunity. Here, we uncovered a distinct CD8+ T cell population expressing the activating natural killer (NK) receptor NKp30 in the peripheral blood of healthy individuals. We revealed that IL-15 could de novo induce NKp30 expression in a pop...

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Main Authors: Correia, Margareta (Author) , Stojanovic, Ana (Author) , Bauer, Katharina (Author) , Juraeva, Dilafruz (Author) , Tykocinski, Lars-Oliver (Author) , Lorenz, Hanns-Martin (Author) , Brors, Benedikt (Author) , Cerwenka, Adelheid (Author)
Format: Article (Journal)
Language:English
Published: [June 26, 2018]
In: Proceedings of the National Academy of Sciences of the United States of America
Year: 2018, Volume: 115, Issue: 26
ISSN:1091-6490
DOI:10.1073/pnas.1720564115
Online Access:Verlag, Volltext: https://doi.org/10.1073/pnas.1720564115
Verlag, Volltext: https://www.pnas.org/content/115/26/E5980
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Author Notes:Margareta P. Correia, Ana Stojanovic, Katharina Bauer, Dilafruz Juraeva, Lars-Oliver Tykocinski, Hanns-Martin Lorenz, Benedikt Brors, Adelheid Cerwenka
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Summary:CD8+ T cells are considered prototypical cells of adaptive immunity. Here, we uncovered a distinct CD8+ T cell population expressing the activating natural killer (NK) receptor NKp30 in the peripheral blood of healthy individuals. We revealed that IL-15 could de novo induce NKp30 expression in a population of CD8+ T cells and drive their differentiation toward a broad innate transcriptional landscape. The adaptor FcεRIγ was concomitantly induced and was shown to be crucial to enable NKp30 cell-surface expression and function in CD8+ T cells. FcεRIγ de novo expression required promoter demethylation and was accompanied by acquisition of the signaling molecule Syk and the “innate” transcription factor PLZF. IL-15-induced NKp30+CD8+ T cells exhibited high NK-like antitumor activity in vitro and were able to synergize with T cell receptor signaling. Importantly, this population potently controlled tumor growth in a preclinical xenograft mouse model. Our study, while blurring the borders between innate and adaptive immunity, reveals a unique NKp30+FcεRIγ+CD8+ T cell population with high antitumor therapeutic potential.
Item Description:Published online June 12, 2018
Gesehen am 28.06.2019
Physical Description:Online Resource
ISSN:1091-6490
DOI:10.1073/pnas.1720564115

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