Metabolic reprogramming of naïve regulatory T cells by IL-7 and IL-15 promotes their persistence and performance upon adoptive transfer
Abstract Tregs for adoptive therapy are traditionally expanded ex vivo using high doses of IL-2. However, the final Treg product has limited survival once infused in patients, potentially affecting therapeutic effectiveness. Here, we tested a novel expansion protocol in which highly purified naïve T...
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| Format: | Article |
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Nature Portfolio
2025-01-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-024-07381-1 |
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| author | Jessica Filoni Arianna Ferrari Tatiana Jofra Anna Rita Putignano Lorenzo Da Dalt Susanna Cesarano Carla Di Dedda Fabrizia Bonacina Federica Marchesi Danilo Norata Chiara Bonini Lorenzo Piemonti Paolo Monti |
| author_facet | Jessica Filoni Arianna Ferrari Tatiana Jofra Anna Rita Putignano Lorenzo Da Dalt Susanna Cesarano Carla Di Dedda Fabrizia Bonacina Federica Marchesi Danilo Norata Chiara Bonini Lorenzo Piemonti Paolo Monti |
| author_sort | Jessica Filoni |
| collection | DOAJ |
| description | Abstract Tregs for adoptive therapy are traditionally expanded ex vivo using high doses of IL-2. However, the final Treg product has limited survival once infused in patients, potentially affecting therapeutic effectiveness. Here, we tested a novel expansion protocol in which highly purified naïve Tregs were expanded with a combination of IL-7 and IL-15, in the absence of IL-2. The final Treg product was enriched with cells displaying an immature CD45RA+CD62L+CD95+ phenotype, reminiscent of conventional memory stem T cells. The combination of IL-7 and IL-15 confers Tregs a glycolytic metabolism and improved metabolic fitness, characterized by an increased capacity to adapt metabolism according to glucose and oxygen availability. Tregs expanded with IL-7 and IL-15 showed longer persistence and an improved capacity to control xeno-GvHD in NSG mice. This work suggests that metabolic reprogramming induced by IL-7 and IL-15 provides better Treg performance for adoptive therapy. |
| format | Article |
| id | doaj-art-c571b10922964db39fcc34229d81c52a |
| institution | Kabale University |
| issn | 2399-3642 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj-art-c571b10922964db39fcc34229d81c52a2025-02-09T12:50:37ZengNature PortfolioCommunications Biology2399-36422025-01-018111010.1038/s42003-024-07381-1Metabolic reprogramming of naïve regulatory T cells by IL-7 and IL-15 promotes their persistence and performance upon adoptive transferJessica Filoni0Arianna Ferrari1Tatiana Jofra2Anna Rita Putignano3Lorenzo Da Dalt4Susanna Cesarano5Carla Di Dedda6Fabrizia Bonacina7Federica Marchesi8Danilo Norata9Chiara Bonini10Lorenzo Piemonti11Paolo Monti12San Raffaele Diabetes Research Institute, IRCCS Ospedale San Raffaele MilanSan Raffaele Diabetes Research Institute, IRCCS Ospedale San Raffaele MilanSan Raffaele Diabetes Research Institute, IRCCS Ospedale San Raffaele MilanDepartment of Immunology and Inflammation, IRCCS Humanitas Research Hospital RozzanoDepartment of Pharmacological and Biomolecular Sciences, Università degli Studi di MilanoExperimental Hematology Unit, IRCCS Ospedale San Raffaele MilanSan Raffaele Diabetes Research Institute, IRCCS Ospedale San Raffaele MilanDepartment of Pharmacological and Biomolecular Sciences, Università degli Studi di MilanoDepartment of Medical Biotechnology and Translational Medicine, University of MilanDepartment of Pharmacological and Biomolecular Sciences, Università degli Studi di MilanoExperimental Hematology Unit, IRCCS Ospedale San Raffaele MilanSan Raffaele Diabetes Research Institute, IRCCS Ospedale San Raffaele MilanSan Raffaele Diabetes Research Institute, IRCCS Ospedale San Raffaele MilanAbstract Tregs for adoptive therapy are traditionally expanded ex vivo using high doses of IL-2. However, the final Treg product has limited survival once infused in patients, potentially affecting therapeutic effectiveness. Here, we tested a novel expansion protocol in which highly purified naïve Tregs were expanded with a combination of IL-7 and IL-15, in the absence of IL-2. The final Treg product was enriched with cells displaying an immature CD45RA+CD62L+CD95+ phenotype, reminiscent of conventional memory stem T cells. The combination of IL-7 and IL-15 confers Tregs a glycolytic metabolism and improved metabolic fitness, characterized by an increased capacity to adapt metabolism according to glucose and oxygen availability. Tregs expanded with IL-7 and IL-15 showed longer persistence and an improved capacity to control xeno-GvHD in NSG mice. This work suggests that metabolic reprogramming induced by IL-7 and IL-15 provides better Treg performance for adoptive therapy.https://doi.org/10.1038/s42003-024-07381-1 |
| spellingShingle | Jessica Filoni Arianna Ferrari Tatiana Jofra Anna Rita Putignano Lorenzo Da Dalt Susanna Cesarano Carla Di Dedda Fabrizia Bonacina Federica Marchesi Danilo Norata Chiara Bonini Lorenzo Piemonti Paolo Monti Metabolic reprogramming of naïve regulatory T cells by IL-7 and IL-15 promotes their persistence and performance upon adoptive transfer Communications Biology |
| title | Metabolic reprogramming of naïve regulatory T cells by IL-7 and IL-15 promotes their persistence and performance upon adoptive transfer |
| title_full | Metabolic reprogramming of naïve regulatory T cells by IL-7 and IL-15 promotes their persistence and performance upon adoptive transfer |
| title_fullStr | Metabolic reprogramming of naïve regulatory T cells by IL-7 and IL-15 promotes their persistence and performance upon adoptive transfer |
| title_full_unstemmed | Metabolic reprogramming of naïve regulatory T cells by IL-7 and IL-15 promotes their persistence and performance upon adoptive transfer |
| title_short | Metabolic reprogramming of naïve regulatory T cells by IL-7 and IL-15 promotes their persistence and performance upon adoptive transfer |
| title_sort | metabolic reprogramming of naive regulatory t cells by il 7 and il 15 promotes their persistence and performance upon adoptive transfer |
| url | https://doi.org/10.1038/s42003-024-07381-1 |
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