Fatty acid metabolism complements glycolysis in the selective regulatory T cell expansion during tumor growth.
Proc Natl Acad Sci U S A
; 115(28): E6546-E6555, 2018 07 10.
Article
em En
| MEDLINE
| ID: mdl-29941600
The tumor microenvironment restrains conventional T cell (Tconv) activation while facilitating the expansion of Tregs. Here we showed that Tregs' advantage in the tumor milieu relies on supplemental energetic routes involving lipid metabolism. In murine models, tumor-infiltrating Tregs displayed intracellular lipid accumulation, which was attributable to an increased rate of fatty acid (FA) synthesis. Since the relative advantage in glucose uptake may fuel FA synthesis in intratumoral Tregs, we demonstrated that both glycolytic and oxidative metabolism contribute to Tregs' expansion. We corroborated our data in human tumors showing that Tregs displayed a gene signature oriented toward glycolysis and lipid synthesis. Our data support a model in which signals from the tumor microenvironment induce a circuitry of glycolysis, FA synthesis, and oxidation that confers a preferential proliferative advantage to Tregs, whose targeting might represent a strategy for cancer treatment.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Linfócitos T Reguladores
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Ácidos Graxos
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Microambiente Tumoral
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Glicólise
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Neoplasias Experimentais
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article