%0 Journal Article
%A Correia, Margareta P
%A Stojanovic, Ana
%A Bauer, Katharina
%A Juraeva, Dilafruz
%A Tykocinski, Lars-Oliver
%A Lorenz, Hanns-Martin
%A Brors, Benedikt
%A Cerwenka, Adelheid
%T Distinct human circulating NKp30+FcεRIγ+CD8+ T cell population exhibiting high natural killer-like antitumor potential.
%J Proceedings of the National Academy of Sciences of the United States of America
%V 115
%N 26
%@ 1091-6490
%C Washington, DC
%I National Acad. of Sciences
%M DKFZ-2018-01469
%P E5980 - E5989
%D 2018
%X 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.
%K FCER1G, human (NLM Chemicals)
%K NCR3 protein, human (NLM Chemicals)
%K Natural Cytotoxicity Triggering Receptor 3 (NLM Chemicals)
%K Receptors, Fc (NLM Chemicals)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:29895693
%2 pmc:PMC6042091
%R 10.1073/pnas.1720564115
%U https://inrepo02.dkfz.de/record/137589