Fatty acid metabolism complements glycolysis in th selective regulatory t cell expansion during tumor growth
MetadataShow full item record
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.
Showing items related by title, author, creator and subject.
Tumor-infiltrating FOXP3<sup>+</sup> T regulatory cells show strong prognostic significance in colorectal cancerSalama, P.; Phillips, M.; Grieu, F.; Morris, M.; Zeps, Nikolajs; Joseph, D.; Platell, C.; Iacopetta, B. (2009)Purpose: To determine the prognostic significance of FOXP3+ lymphocyte (Treg) density in colorectal cancer compared with conventional histopathologic features and with CD8+ and CD45RO+ lymphocyte densities. Patients and ...
Impaired function of regulatory T-cells in patients with chronic obstructive pulmonary disease (COPD)Tan, D.; Fernandez, S.; Price, Patricia; French, M.; Thompson, P.; Moodley, Y. (2014)Anti-inflammatory pathways affecting chronic obstructive pulmonary disease (COPD) are poorly understood. Regulatory T-cells (Tregs) are important negative regulators of T-cell activity and hence were investigated in COPD ...
Peak inflammation in atherosclerosis, primary biliary cirrhosis and autoimmune arthritis is counter-intuitively associated with regulatory T cell enrichmentGaretto, S.; Trovato, A.; Lleo, A.; Sala, F.; Martini, E.; Betz, A.; Norata, Giuseppe; Invernizzi, P.; Kallikourdis, M. (2015)© 2015 The Authors. Regulatory T cells (Treg) influence the development of autoimmunity and their use is increasingly proposed for clinical applications. The well-characterized suppressive potential of Treg frequently ...