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Fatty acid metabolism complements glycolysis in the selective regulatory T cell expansion during tumor growth
- Source :
- Proceedings of the National Academy of Sciences of the United States of America, Proceedings of the National Academy of Sciences of the United States of America, 2018, 115 (28), pp.E6546-E6555. ⟨10.1073/pnas.1720113115⟩, Proceedings of the National Academy of Sciences of the United States of America (Online) 115 (2018): E6546–E6555. doi:10.1073/pnas.1720113115, info:cnr-pdr/source/autori:Pacella I.; Procaccini C.; Focaccetti C.; Miacci S.; Timperi E.; Faicchia D.; Severa M.; Rizzo F.; Coccia E.M.; Bonacina F.; Mitro N.; Norata G.D.; Rossetti G.; Ranzani V.; Pagani M.; Giorda E.; Wei Y.; Matarese G.; Barnaba V.; Piconese S./titolo:Fatty acid metabolism complements glycolysis in th selective regulatory t cell expansion during tumor growth/doi:10.1073%2Fpnas.1720113115/rivista:Proceedings of the National Academy of Sciences of the United States of America (Online)/anno:2018/pagina_da:E6546/pagina_a:E6555/intervallo_pagine:E6546–E6555/volume:115, Proceedings of the National Academy of Sciences of the United States of America, National Academy of Sciences, 2018, 115 (28), pp.E6546-E6555. ⟨10.1073/pnas.1720113115⟩
- Publication Year :
- 2018
- Publisher :
- HAL CCSD, 2018.
-
Abstract
- International audience; 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.
- Subjects :
- 0301 basic medicine
MESH: Neoplasm Proteins
MESH: Oxidation-Reduction
Treg
fatty acid synthesis
glycolysis
ox40
tumor microenvironment
Glycolysi
T-Lymphocytes
Type I
Settore MED/04
T-Lymphocytes, Regulatory
Transgenic
chemistry.chemical_compound
Mice
0302 clinical medicine
Neoplasms
MESH: Tumor Microenvironment
Glycolysis
MESH: Animals
Tumor
Multidisciplinary
Chemistry
Fatty Acids
hemic and immune systems
Regulatory
Cell biology
Neoplasm Proteins
MESH: Fatty Acids
Fatty Acid Synthase, Type I
medicine.anatomical_structure
MESH: Neoplasms, Experimental
PNAS Plus
Fatty Acid Synthase
030220 oncology & carcinogenesis
MESH: Glycolysis
[SDV.IMM]Life Sciences [q-bio]/Immunology
MESH: Fatty Acid Synthase, Type I
Fatty acid synthesis
Ox40
Tumor microenvironment
Animals
Cell Line, Tumor
Humans
Mice, Transgenic
Neoplasms, Experimental
Oxidation-Reduction
Tumor Microenvironment
Intracellular
MESH: Cell Line, Tumor
[SDV.IMM] Life Sciences [q-bio]/Immunology
Regulatory T cell
MESH: Mice, Transgenic
T cell
chemical and pharmacologic phenomena
Cell Line
03 medical and health sciences
Experimental
Fatty acid synthesi
medicine
MESH: Mice
MESH: Humans
Fatty acid metabolism
MESH: T-Lymphocytes, Regulatory
Lipid metabolism
030104 developmental biology
Subjects
Details
- Language :
- English
- ISSN :
- 00278424 and 10916490
- Database :
- OpenAIRE
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America, Proceedings of the National Academy of Sciences of the United States of America, 2018, 115 (28), pp.E6546-E6555. ⟨10.1073/pnas.1720113115⟩, Proceedings of the National Academy of Sciences of the United States of America (Online) 115 (2018): E6546–E6555. doi:10.1073/pnas.1720113115, info:cnr-pdr/source/autori:Pacella I.; Procaccini C.; Focaccetti C.; Miacci S.; Timperi E.; Faicchia D.; Severa M.; Rizzo F.; Coccia E.M.; Bonacina F.; Mitro N.; Norata G.D.; Rossetti G.; Ranzani V.; Pagani M.; Giorda E.; Wei Y.; Matarese G.; Barnaba V.; Piconese S./titolo:Fatty acid metabolism complements glycolysis in th selective regulatory t cell expansion during tumor growth/doi:10.1073%2Fpnas.1720113115/rivista:Proceedings of the National Academy of Sciences of the United States of America (Online)/anno:2018/pagina_da:E6546/pagina_a:E6555/intervallo_pagine:E6546–E6555/volume:115, Proceedings of the National Academy of Sciences of the United States of America, National Academy of Sciences, 2018, 115 (28), pp.E6546-E6555. ⟨10.1073/pnas.1720113115⟩
- Accession number :
- edsair.doi.dedup.....17c46c9af26d20583ae98adc1a1c1abd