Journal Article

DKFZ-2018-01469

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Distinct human circulating NKp30+FcεRIγ+CD8+ T cell population exhibiting high natural killer-like antitumor potential.

Correia, M. P. (First author) ; Stojanovic, A.DKFZ* ; Bauer, K.DKFZ* ; Juraeva, D.DKFZ* ; Tykocinski, L.-O. ; Lorenz, H.-M. ; Brors, B.DKFZ* ; Cerwenka, A. (Last author)DKFZ*

2018
National Acad. of Sciences Washington, DC

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Please use a persistent id in citations: doi:10.1073/pnas.1720564115

Abstract: 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.

Keyword(s): FCER1G, human ; NCR3 protein, human ; Natural Cytotoxicity Triggering Receptor 3 ; Receptors, Fc

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Contributing Institute(s):

1. Nachwuchsgruppe Angeborene Immunität (D080)
2. Angewandte Bioinformatik (G200)
3. DKTK Heidelberg (L101)

Research Program(s):

1. 314 - Tumor immunology (POF3-314) (POF3-314)

Appears in the scientific report 2018

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Database coverage:
; BIOSIS Previews ; Current Contents - Agriculture, Biology and Environmental Sciences ; Current Contents - Life Sciences ; Ebsco Academic Search ; IF >= 5 ; JCR ; NCBI Molecular Biology Database ; National-Konsortium ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Thomson Reuters Master Journal List ; Web of Science Core Collection ; Zoological Record

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