| First Author | Yan H | Year | 2023 |
| Journal | iScience | Volume | 26 |
| Issue | 11 | Pages | 108087 |
| PubMed ID | 37860697 | Mgi Jnum | J:352699 |
| Mgi Id | MGI:7663306 | Doi | 10.1016/j.isci.2023.108087 |
| Citation | Yan H, et al. (2023) The transcription factor IRF4 determines the anti-tumor immunity of CD8(+) T cells. iScience 26(11):108087 |
| abstractText | Understanding the factors that regulate T cell infiltration and functional states in solid tumors is crucial for advancing cancer immunotherapies. Here, we discovered that the expression of interferon regulatory factor 4 (IRF4) was a critical T cell intrinsic requirement for effective anti-tumor immunity. Mice with T-cell-specific ablation of IRF4 showed significantly reduced T cell tumor infiltration and function, resulting in accelerated growth of subcutaneous syngeneic tumors and allowing the growth of allogeneic tumors. Additionally, engineered overexpression of IRF4 in anti-tumor CD8(+) T cells that were adoptively transferred significantly promoted their tumor infiltration and transition from a naive/memory-like cell state into effector T cell states. As a result, IRF4-engineered anti-tumor T cells exhibited significantly improved anti-tumor efficacy, and inhibited tumor growth either alone or in combination with PD-L1 blockade. These findings identify IRF4 as a crucial cell-intrinsic driver of T cell infiltration and function in tumors, emphasizing the potential of IRF4-engineering as an immunotherapeutic approach. |
