| First Author | Wang D | Year | 2018 |
| Journal | Cell Rep | Volume | 23 |
| Issue | 11 | Pages | 3262-3274 |
| PubMed ID | 29898397 | Mgi Jnum | J:270788 |
| Mgi Id | MGI:6278724 | Doi | 10.1016/j.celrep.2018.05.050 |
| Citation | Wang D, et al. (2018) Targeting EZH2 Reprograms Intratumoral Regulatory T Cells to Enhance Cancer Immunity. Cell Rep 23(11):3262-3274 |
| abstractText | Regulatory T cells (Tregs) are critical for maintaining immune homeostasis, but their presence in tumor tissues impairs anti-tumor immunity and portends poor prognoses in cancer patients. Here, we reveal a mechanism to selectively target and reprogram the function of tumor-infiltrating Tregs (TI-Tregs) by exploiting their dependency on the histone H3K27 methyltransferase enhancer of zeste homolog 2 (EZH2) in tumors. Disruption of EZH2 activity in Tregs, either pharmacologically or genetically, drove the acquisition of pro-inflammatory functions in TI-Tregs, remodeling the tumor microenvironment and enhancing the recruitment and function of CD8(+) and CD4(+) effector T cells that eliminate tumors. Moreover, abolishing EZH2 function in Tregs was mechanistically distinct from, more potent than, and less toxic than a generalized Treg depletion approach. This study reveals a strategy to target Tregs in cancer that mitigates autoimmunity by reprogramming their function in tumors to enhance anti-cancer immunity. |
