TY  - JOUR
AU  - Correia, Margareta P
AU  - Stojanovic, Ana
AU  - Bauer, Katharina
AU  - Juraeva, Dilafruz
AU  - Tykocinski, Lars-Oliver
AU  - Lorenz, Hanns-Martin
AU  - Brors, Benedikt
AU  - Cerwenka, Adelheid
TI  - Distinct human circulating NKp30+FcεRIγ+CD8+ T cell population exhibiting high natural killer-like antitumor potential.
JO  - Proceedings of the National Academy of Sciences of the United States of America
VL  - 115
IS  - 26
SN  - 1091-6490
CY  - Washington, DC
PB  - National Acad. of Sciences
M1  - DKFZ-2018-01469
SP  - E5980 - E5989
PY  - 2018
AB  - 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.
KW  - FCER1G, human (NLM Chemicals)
KW  - NCR3 protein, human (NLM Chemicals)
KW  - Natural Cytotoxicity Triggering Receptor 3 (NLM Chemicals)
KW  - Receptors, Fc (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:29895693
C2  - pmc:PMC6042091
DO  - DOI:10.1073/pnas.1720564115
UR  - https://inrepo02.dkfz.de/record/137589
ER  -