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: | , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
[June 26, 2018]
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| 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 |
MARC
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| 245 | 1 | 0 | |a Distinct human circulating NKp30+FcεRIγ+CD8+ T cell population exhibiting high natural killer-like antitumor potential |c Margareta P. Correia, Ana Stojanovic, Katharina Bauer, Dilafruz Juraeva, Lars-Oliver Tykocinski, Hanns-Martin Lorenz, Benedikt Brors, Adelheid Cerwenka |
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| 520 | |a 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. | ||
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