Modulation of mTOR Signalling Triggers the Formation of Stem Cell-like Memory T Cells.

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State: Public
Version: author
License: CC BY-NC-ND 4.0
Serval ID
serval:BIB_20C77B24FA47
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Modulation of mTOR Signalling Triggers the Formation of Stem Cell-like Memory T Cells.
Journal
Ebiomedicine
Author(s)
Scholz G., Jandus C., Zhang L., Grandclément C., Lopez-Mejia I.C., Soneson C., Delorenzi M., Fajas L., Held W., Dormond O., Romero P.
ISSN
2352-3964 (Electronic)
ISSN-L
2352-3964
Publication state
Published
Issued date
2016
Volume
4
Pages
50-61
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't Publication Status: epublish
Abstract
Robust, long-lasting immune responses are elicited by memory T cells that possess properties of stem cells, enabling them to persist long-term and to permanently replenish the effector pools. Thus, stem cell-like memory T (TSCM) cells are of key therapeutic value and efforts are underway to characterize TSCM cells and to identify means for their targeted induction. Here, we show that inhibition of mechanistic/mammalian Target of Rapamycin (mTOR) complex 1 (mTORC1) by rapamycin or the Wnt-β-catenin signalling activator TWS119 in activated human naive T cells leads to the induction of TSCM cells. We show that these compounds switch T cell metabolism to fatty acid oxidation as favoured metabolic programme for TSCM cell generation. Of note, pharmacologically induced TSCM cells possess superior functional features as a long-term repopulation capacity after adoptive transfer. Furthermore, we provide insights into the transcriptome of TSCM cells. Our data identify a mechanism of pharmacological mTORC1 inhibitors, allowing us to confer stemness to human naive T cells which may be significantly relevant for the design of innovative T cell-based cancer immunotherapies.
Pubmed
Web of science
Open Access
Yes
Create date
01/11/2016 22:56
Last modification date
09/09/2020 6:08
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