Geltink, Ramon I. Klein, Edwards-Hicks, Joy ORCID: 0000-0002-9313-5718, Apostolova, Petya, O'Sullivan, David, Sanin, David E., Patterson, Annette E., Puleston, Daniel J., Ligthart, Nina A. M., Buescher, Joerg M., Grzes, Katarzyna M., Kabat, Agnieszka M., Stanczak, Michal, Curtis, Jonathan D., Hassler, Fabian, Uhl, Franziska M., Fabri, Mario, Zeiser, Robert, Pearce, Edward J. and Pearce, Erika L. (2020). Metabolic conditioning of CD8(+) effector T cells for adoptive cell therapy. Nat. Metab., 2 (8). S. 703 - 725. BERLIN: NATURE RESEARCH. ISSN 2522-5812

Full text not available from this repository.

Abstract

CD8(+) effector T (T-E) cell proliferation and cytokine production depends on enhanced glucose metabolism. However, circulating T cells continuously adapt to glucose fluctuations caused by diet and inter-organ metabolite exchange. Here we show that transient glucose restriction (TGR) in activated CD8(+) T-E cells metabolically primes effector functions and enhances tumour clearance in mice. Tumour-specific TGR CD8(+) T-E cells co-cultured with tumour spheroids in replete conditions display enhanced effector molecule expression, and adoptive transfer of these cells in a murine lymphoma model leads to greater numbers of immunologically functional circulating donor cells and complete tumour clearance. Mechanistically, T-E cells treated with TGR undergo metabolic remodelling that, after glucose re-exposure, supports enhanced glucose uptake, increased carbon allocation to the pentose phosphate pathway (PPP) and a cellular redox shift towards a more reduced state-all indicators of a more anabolic programme to support their enhanced functionality. Thus, metabolic conditioning could be used to promote efficiency of T-cell products for adoptive cellular therapy.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Geltink, Ramon I. KleinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Edwards-Hicks, JoyUNSPECIFIEDorcid.org/0000-0002-9313-5718UNSPECIFIED
Apostolova, PetyaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
O'Sullivan, DavidUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sanin, David E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Patterson, Annette E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Puleston, Daniel J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ligthart, Nina A. M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Buescher, Joerg M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Grzes, Katarzyna M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kabat, Agnieszka M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stanczak, MichalUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Curtis, Jonathan D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hassler, FabianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Uhl, Franziska M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fabri, MarioUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zeiser, RobertUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pearce, Edward J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pearce, Erika L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-324792
DOI: 10.1038/s42255-020-0256-z
Journal or Publication Title: Nat. Metab.
Volume: 2
Number: 8
Page Range: S. 703 - 725
Date: 2020
Publisher: NATURE RESEARCH
Place of Publication: BERLIN
ISSN: 2522-5812
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
TUMOR MICROENVIRONMENT; GLUCOSE-METABOLISM; ACTIVATION; MEMORY; MASS; LYMPHOCYTES; SENSOR; GLUT1Multiple languages
Endocrinology & MetabolismMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/32479

Downloads

Downloads per month over past year

Altmetric

Export

Actions (login required)

View Item View Item