GSE152018 Metabolic conditioning of CD8+ effector T cells for adoptive cell therapy

Contributors : Ramon I Klein Geltink ; Joy Edwards-Hicks ; Petya Apostolova ; David O ’Sullivan ; David E Sanin ; Annette E Patterson ; Daniel J Puleston ; Nina A Ligthart ; Joerg M Buesscher ; Katarzyna Grzes ; Agnieska Kabat ; Michal Stanczak ; Jonathan D Curtis ; Fabian Haessler ; Franziska M Uhl ; Mario Fabri ; Robert Zeiser ; Edward J Pearce ; Erika L PearceSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusEffector CD8+ T cell (TE) 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 metabolically primes effector functions and enhances tumour clearance in mice. Tumor-specific TGR CD8+ TE co-cultured with tumor 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 tumor clearance. Mechanistically, TGR TE undergo metabolic remodelling that upon glucose re-exposure supports enhanced glucose uptake, increased carbon allocation to the pentose phosphate pathway (PPP), and a cellular redox shift toward a more reduced state, all indicators of a more anabolic program to support their enhanced functionality. Thus, metabolic conditioning...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Mus musculus Source Type: research