In:
Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 115, No. 26 ( 2018-06-26)
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.
Type of Medium:
Online Resource
ISSN:
0027-8424
,
1091-6490
DOI:
10.1073/pnas.1720564115
Language:
English
Publisher:
Proceedings of the National Academy of Sciences
Publication Date:
2018
detail.hit.zdb_id:
209104-5
detail.hit.zdb_id:
1461794-8
SSG:
11
SSG:
12
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