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  Metabolic conditioning of CD8+ effector T cells for adoptive cell therapy

Klein-Geltink, R., Edwards-Hicks, J., Apostolova, P., O'Sullivan, D., Sanin, P. D. E., Annette, E. P., et al. (2020). Metabolic conditioning of CD8+ effector T cells for adoptive cell therapy. Nature Metabolism. doi:doi.org/10.1038/s42255-020-0256-z.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0006-CF32-9 Version Permalink: http://hdl.handle.net/21.11116/0000-0006-CF33-8
Genre: Journal Article

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Klein-Geltink, Ramon1, Author              
Edwards-Hicks, Joy1, Author
Apostolova, Petya1, Author
O'Sullivan, David1, Author              
Sanin, Pena David Estaban1, Author              
Annette, Elizabeth Patterson1, Author              
Puleston, Daniel1, Author              
Ligthart, Nina A. M.1, Author
Büscher, Jörg Martin1, Author              
Grzes, Katarzyna1, Author              
Kabat, Agnieska1, Author              
Stanczak, Michal2, Author
Curtis, Jonathen1, Author
Hässler, Fabian1, Author
Uhl, Franziska M.2, Author
Fabri, Mario2, Author
Zeiser, Robert2, Author
Pearce, Edward J.1, Author              
Pearce, Erika L.1, Author              
Affiliations:
1Department Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, ou_2243648              
2External Organizations, ou_persistent22              

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 Abstract: CD8+ effector T (TE) 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+ TE cells metabolically primes effector functions and enhances tumour clearance in mice. Tumour-specific TGR CD8+ TE 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, TE 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.

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Language(s): eng - English
 Dates: 2020-08-03
 Publication Status: Published online
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 Rev. Method: Peer
 Identifiers: DOI: doi.org/10.1038/s42255-020-0256-z
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Title: Nature Metabolism
Source Genre: Journal
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