De novo NAD+ synthesis contributes to CD8+ T cell metabolic fitness and antitumor function
Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved..
The dysfunction and clonal constriction of tumor-infiltrating CD8+ T cells are accompanied by alterations in cellular metabolism; however, how the cell-intrinsic metabolic pathway specifies intratumoral CD8+ T cell features remains elusive. Here, we show that cell-autonomous generation of nicotinamide adenine dinucleotide (NAD+) via the kynurenine pathway (KP) contributes to the maintenance of intratumoral CD8+ T cell metabolic and functional fitness. De novo NAD+ synthesis is involved in CD8+ T cell metabolism and antitumor function. KP-derived NAD+ promotes PTEN deacetylation, thereby facilitating PTEN degradation and preventing PTEN-dependent metabolic defects. Importantly, impaired cell-autonomous NAD+ synthesis limits CD8+ T cell responses in human colorectal cancer samples. Our results reveal that KP-derived NAD+ regulates the CD8+ T cell metabolic and functional state by restricting PTEN activity and suggest that modulation of de novo NAD+ synthesis could restore CD8+ T cell metabolic fitness and antitumor function.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:42 |
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| Enthalten in: |
Cell reports - 42(2023), 12 vom: 26. Dez., Seite 113518 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Wan, Jie [VerfasserIn] |
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| Links: |
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| Themen: |
0U46U6E8UK |
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| Anmerkungen: |
Date Completed 01.01.2024 Date Revised 26.01.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.celrep.2023.113518 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM365328006 |
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| 500 | |a published: Print-Electronic | ||
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| 520 | |a Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a The dysfunction and clonal constriction of tumor-infiltrating CD8+ T cells are accompanied by alterations in cellular metabolism; however, how the cell-intrinsic metabolic pathway specifies intratumoral CD8+ T cell features remains elusive. Here, we show that cell-autonomous generation of nicotinamide adenine dinucleotide (NAD+) via the kynurenine pathway (KP) contributes to the maintenance of intratumoral CD8+ T cell metabolic and functional fitness. De novo NAD+ synthesis is involved in CD8+ T cell metabolism and antitumor function. KP-derived NAD+ promotes PTEN deacetylation, thereby facilitating PTEN degradation and preventing PTEN-dependent metabolic defects. Importantly, impaired cell-autonomous NAD+ synthesis limits CD8+ T cell responses in human colorectal cancer samples. Our results reveal that KP-derived NAD+ regulates the CD8+ T cell metabolic and functional state by restricting PTEN activity and suggest that modulation of de novo NAD+ synthesis could restore CD8+ T cell metabolic fitness and antitumor function | ||
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| 700 | 1 | |a Hu, Jiajia |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Haiyan |e verfasserin |4 aut | |
| 700 | 1 | |a Han, Qiaoqiao |e verfasserin |4 aut | |
| 700 | 1 | |a Jie, Zuliang |e verfasserin |4 aut | |
| 700 | 1 | |a Zou, Qiang |e verfasserin |4 aut | |
| 700 | 1 | |a Shi, Jian-Hong |e verfasserin |4 aut | |
| 700 | 1 | |a Yu, Xiaoyan |e verfasserin |4 aut | |
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