Fatty acid metabolism complements glycolysis in th selective regulatory t cell expansion during tumor growth
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 int...
| Main Authors: | , , , , , , , , , , , , , , , , , , , |
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| Format: | Journal Article |
| Published: |
National Academy of Sciences
2018
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| Online Access: | http://hdl.handle.net/20.500.11937/69468 |
| _version_ | 1848762049174175744 |
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| author | Pacella, I. Procaccini, C. Focaccetti, C. Miacci, S. Timperi, E. Faicchia, D. Severa, M. Rizzo, F. Coccia, E. Bonacina, F. Mitro, N. Norata, Giuseppe Rossetti, G. Ranzani, V. Pagani, M. Giorda, E. Wei, Y. Matarese, G. Barnaba, V. Piconese, S. |
| author_facet | Pacella, I. Procaccini, C. Focaccetti, C. Miacci, S. Timperi, E. Faicchia, D. Severa, M. Rizzo, F. Coccia, E. Bonacina, F. Mitro, N. Norata, Giuseppe Rossetti, G. Ranzani, V. Pagani, M. Giorda, E. Wei, Y. Matarese, G. Barnaba, V. Piconese, S. |
| author_sort | Pacella, I. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | 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. |
| first_indexed | 2025-11-14T10:41:23Z |
| format | Journal Article |
| id | curtin-20.500.11937-69468 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T10:41:23Z |
| publishDate | 2018 |
| publisher | National Academy of Sciences |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-694682018-10-12T01:26:03Z Fatty acid metabolism complements glycolysis in th selective regulatory t cell expansion during tumor growth Pacella, I. Procaccini, C. Focaccetti, C. Miacci, S. Timperi, E. Faicchia, D. Severa, M. Rizzo, F. Coccia, E. Bonacina, F. Mitro, N. Norata, Giuseppe Rossetti, G. Ranzani, V. Pagani, M. Giorda, E. Wei, Y. Matarese, G. Barnaba, V. Piconese, S. 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. 2018 Journal Article http://hdl.handle.net/20.500.11937/69468 10.1073/pnas.1720113115 National Academy of Sciences fulltext |
| spellingShingle | Pacella, I. Procaccini, C. Focaccetti, C. Miacci, S. Timperi, E. Faicchia, D. Severa, M. Rizzo, F. Coccia, E. Bonacina, F. Mitro, N. Norata, Giuseppe Rossetti, G. Ranzani, V. Pagani, M. Giorda, E. Wei, Y. Matarese, G. Barnaba, V. Piconese, S. Fatty acid metabolism complements glycolysis in th selective regulatory t cell expansion during tumor growth |
| title | Fatty acid metabolism complements glycolysis in th selective regulatory t cell expansion during tumor growth |
| title_full | Fatty acid metabolism complements glycolysis in th selective regulatory t cell expansion during tumor growth |
| title_fullStr | Fatty acid metabolism complements glycolysis in th selective regulatory t cell expansion during tumor growth |
| title_full_unstemmed | Fatty acid metabolism complements glycolysis in th selective regulatory t cell expansion during tumor growth |
| title_short | Fatty acid metabolism complements glycolysis in th selective regulatory t cell expansion during tumor growth |
| title_sort | fatty acid metabolism complements glycolysis in th selective regulatory t cell expansion during tumor growth |
| url | http://hdl.handle.net/20.500.11937/69468 |