Distinct human circulating NKp30+FcεRIγ+CD8+ T cell population exhibiting high natural killer-like antitumor potential

• Verfasst von: Correia, Margareta [VerfasserIn]
• Verfasst von: Stojanovic, Ana [VerfasserIn]
• Verfasst von: Bauer, Katharina [VerfasserIn]
• Verfasst von: Juraeva, Dilafruz [VerfasserIn]
• Verfasst von: Tykocinski, Lars-Oliver [VerfasserIn]
• Verfasst von: Lorenz, Hanns-Martin [VerfasserIn]
• Verfasst von: Brors, Benedikt [VerfasserIn]
• Verfasst von: Cerwenka, Adelheid [VerfasserIn]
• Titel: Distinct human circulating NKp30+FcεRIγ+CD8+ T cell population exhibiting high natural killer-like antitumor potential
• Verf.angabe: Margareta P. Correia, Ana Stojanovic, Katharina Bauer, Dilafruz Juraeva, Lars-Oliver Tykocinski, Hanns-Martin Lorenz, Benedikt Brors, Adelheid Cerwenka
• E-Jahr: 2018
• Jahr: [June 26, 2018]
• Umfang: 10 S.
• Fussnoten: Published online June 12, 2018 ; Gesehen am 28.06.2019
• Titel Quelle: Enthalten in: National Academy of Sciences (Washington, DC)Proceedings of the National Academy of Sciences of the United States of America
• Ort Quelle: Washington, DC : National Acad. of Sciences, 1915
• Jahr Quelle: 2018
• Band/Heft Quelle: 115 (2018,26), Seite E5980-E5989, 10 Seiten
• ISSN Quelle: 1091-6490
• DOI: doi:10.1073/pnas.1720564115
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: anti-tumor
• Sach-SW: CD8+ T cells
• Sach-SW: IL-15
• Sach-SW: innate
• Sach-SW: NKp30
• K10plus-PPN: 1668116359

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.