| First Author | Chatterjee S | Year | 2018 |
| Journal | Cell Metab | Volume | 27 |
| Issue | 1 | Pages | 85-100.e8 |
| PubMed ID | 29129787 | Mgi Jnum | J:256862 |
| Mgi Id | MGI:6115115 | Doi | 10.1016/j.cmet.2017.10.006 |
| Citation | Chatterjee S, et al. (2018) CD38-NAD(+)Axis Regulates Immunotherapeutic Anti-Tumor T Cell Response. Cell Metab 27(1):85-100.e8 |
| abstractText | Heightened effector function and prolonged persistence, the key attributes of Th1 and Th17 cells, respectively, are key features of potent anti-tumor T cells. Here, we established ex vivo culture conditions to generate hybrid Th1/17 cells, which persisted long-term in vivo while maintaining their effector function. Using transcriptomics and metabolic profiling approaches, we showed that the enhanced anti-tumor property of Th1/17 cells was dependent on the increased NAD(+)-dependent activity of the histone deacetylase Sirt1. Pharmacological or genetic inhibition of Sirt1 activity impaired the anti-tumor potential of Th1/17 cells. Importantly, T cells with reduced surface expression of the NADase CD38 exhibited intrinsically higher NAD(+), enhanced oxidative phosphorylation, higher glutaminolysis, and altered mitochondrial dynamics that vastly improved tumor control. Lastly, blocking CD38 expression improved tumor control even when using Th0 anti-tumor T cells. Thus, strategies targeting the CD38-NAD(+) axis could increase the efficacy of anti-tumor adoptive T cell therapy. |
