| First Author | Wang F | Year | 2021 |
| Journal | J Clin Invest | Volume | 131 |
| Issue | 19 | PubMed ID | 34403361 |
| Mgi Jnum | J:340069 | Mgi Id | MGI:7520670 |
| Doi | 10.1172/JCI144318 | Citation | Wang F, et al. (2021) ZFP91 disturbs metabolic fitness and antitumor activity of tumor-infiltrating T cells. J Clin Invest 131(19):e144318 |
| abstractText | Proper metabolic activities facilitate T cell expansion and antitumor function; however, the mechanisms underlying disruption of the T cell metabolic program and function in the tumor microenvironment (TME) remain elusive. Here, we show a zinc finger protein 91-governed (ZFP91-governed) mechanism that disrupts the metabolic pathway and antitumor activity of tumor-infiltrating T cells. Single-cell RNA-Seq revealed that impairments in T cell proliferation and activation correlated with ZFP91 in tissue samples from patients with colorectal cancer. T cell-specific deletion of Zfp91 in mice led to enhanced T cell proliferation and potentiated T cell antitumor function. Loss of ZFP91 increased mammalian target of rapamycin complex 1 (mTORC1) activity to drive T cell glycolysis. Mechanistically, T cell antigen receptor-dependent (TCR-dependent) ZFP91 cytosolic translocation promoted protein phosphatase 2A (PP2A) complex assembly, thereby restricting mTORC1-mediated metabolic reprogramming. Our results demonstrate that ZFP91 perturbs T cell metabolic and functional states in the TME and suggest that targeting ZFP91 may improve the efficacy of cancer immunotherapy. |
