| First Author | Wan J | Year | 2023 |
| Journal | Cell Rep | Volume | 42 |
| Issue | 12 | Pages | 113518 |
| PubMed ID | 38041812 | Mgi Jnum | J:343427 |
| Mgi Id | MGI:7567239 | Doi | 10.1016/j.celrep.2023.113518 |
| Citation | Wan J, et al. (2023) De novo NAD(+) synthesis contributes to CD8(+) T cell metabolic fitness and antitumor function. Cell Rep 42(12):113518 |
| abstractText | 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. |
