| First Author | Lee M | Year | 2021 |
| Journal | Cancer Res | Volume | 81 |
| Issue | 8 | Pages | 1965-1976 |
| PubMed ID | 33589517 | Mgi Jnum | J:305554 |
| Mgi Id | MGI:6706802 | Doi | 10.1158/0008-5472.CAN-20-3213 |
| Citation | Lee M, et al. (2021) Tet2 inactivation enhances the anti-tumor activity of tumor-infiltrating lymphocytes. Cancer Res |
| abstractText | Inactivation of tumor-infiltrating lymphocytes (TIL) is one of the mechanisms mitigating anti-tumor immunity during tumor onset and progression. Epigenetic abnormalities are regarded as a major culprit contributing to the dysfunction of TILs within tumor microenvironments. In this study, we used a murine model of melanoma to discover that Tet2 inactivation significantly enhances the anti-tumor activity of TILs with an efficacy comparable to immune checkpoint inhibition imposed by anti-PD-L1 treatment. Single-cell RNA-seq analysis suggested that Tet2-deficient TILs exhibit effector-like features. Transcriptomic and ATAC-seq analysis showed that Tet2 ablation reshapes chromatin accessibility and favors binding of transcription factors geared toward CD8+ T cell activation. Furthermore, the ETS family of transcription factors contributed to augmented CD8+ T cell function following Tet2 depletion. Overall, our study establishes that Tet2 constitutes one of the epigenetic barriers that account for dysfunction of TILs, and that Tet2 inactivation could promote anti-tumor immunity to suppress tumor growth. |
