Fatty acid metabolism complements glycolysis in the selective regulatory T cell expansion during tumor growth.

Abstract:

: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.

authors

Pacella I,Procaccini C,Focaccetti C,Miacci S,Timperi E,Faicchia D,Severa M,Rizzo F,Coccia EM,Bonacina F,Mitro N,Norata GD,Rossetti G,Ranzani V,Pagani M,Giorda E,Wei Y,Matarese G,Barnaba V,Piconese S

doi

10.1073/pnas.1720113115

subject

Has Abstract

pub_date

2018-07-10 00:00:00

pages

E6546-E6555

issue

28

eissn

0027-8424

issn

1091-6490

pii

1720113115

journal_volume

115

pub_type

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