| First Author | Denk D | Year | 2022 |
| Journal | Immunity | Volume | 55 |
| Issue | 11 | Pages | 2059-2073.e8 |
| PubMed ID | 36351375 | Mgi Jnum | J:331111 |
| Mgi Id | MGI:7386638 | Doi | 10.1016/j.immuni.2022.09.014 |
| Citation | Denk D, et al. (2022) Expansion of T memory stem cells with superior anti-tumor immunity by Urolithin A-induced mitophagy. Immunity 55(11):2059-2073.e8 |
| abstractText | T memory stem cells (T(SCM)) display increased self-renewal and prolonged survival capabilities, thus preventing T cell exhaustion and promoting effective anti-tumor T cell responses. T(SCM) cells can be expanded by Urolithin A (UA), which is produced by the commensal gut microbiome from foods rich in ellagitannins and is known to improve mitochondrial health. Oral UA administration to tumor-bearing mice conferred strong anti-tumor CD8(+) T cell immunity, whereas ex vivo UA pre-treated T cells displayed improved anti-tumor function upon adoptive cell transfer. UA-induced T(SCM) formation depended on Pink1-mediated mitophagy triggering cytosolic release of the mitochondrial phosphatase Pgam5. Cytosolic Pgam5 dephosphorylated beta-catenin, which drove Wnt signaling and compensatory mitochondrial biogenesis. Collectively, we unravel a critical signaling pathway linking mitophagy to T(SCM) formation and suggest that the well-tolerated metabolic compound UA represents an attractive option to improve immune therapy. |
