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Journal Article

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

MPS-Authors
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Klein-Geltink,  Ramon
Department Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Edwards-Hicks,  Joy
Department Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Apostolova,  Petya
Department Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

/persons/resource/persons201374

O'Sullivan,  David
Department Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

/persons/resource/persons201442

Sanin,  Pena David Estaban
Department Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Annette,  Elizabeth Patterson
Department Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Puleston,  Daniel
Department Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Ligthart,  Nina A. M.
Department Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Büscher,  Jörg Martin
Department Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

/persons/resource/persons204377

Grzes,  Katarzyna
Department Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

/persons/resource/persons204379

Kabat,  Agnieska
Department Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Curtis,  Jonathen
Department Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Hässler,  Fabian
Department Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Pearce,  Edward J.
Department Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Pearce,  Erika L.
Department Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

External Resource

https://www.nature.com/articles/s42255-020-0256-z
(Publisher version)

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Citation

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, 2, 703-716. doi:doi.org/10.1038/s42255-020-0256-z.


Cite as: https://hdl.handle.net/21.11116/0000-0006-CF32-9
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.