| First Author | Klein Geltink RI | Year | 2020 |
| Journal | Nat Metab | Volume | 2 |
| Issue | 8 | Pages | 703-716 |
| PubMed ID | 32747793 | Mgi Jnum | J:354280 |
| Mgi Id | MGI:7730940 | Doi | 10.1038/s42255-020-0256-z |
| Citation | Klein Geltink RI, et al. (2020) Metabolic conditioning of CD8(+) effector T cells for adoptive cell therapy. Nat Metab 2(8):703-716 |
| abstractText | 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. |
