Tet2 Inactivation Enhances the Anti-Tumor Activity of Tumor-Infiltrating Lymphocytes (TILs) to Curtail Melanoma Growth Academic Article uri icon

abstract

  • Inactivation of tumor infiltrating lymphocytes (TILs) 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 the efficacy comparable to immune checkpoint inhibition imposed by anti-PD-L1 treatment. Single-cell RNA-seq analysis further revealed that Tet2-deficient TILs exhibit effector-like features. Transcriptomic and ATAC-seq analysis further demonstrated that Tet2 deletion reshapes the chromatin accessibility and favors the binding of transcription factors geared toward CD8+ T cell activation. In summary, our study establishes that Tet2 constitutes one of the epigenetic barriers contributing to dysfunction of TILs, and that Tet2 inactivation could benefit anti-tumor immunity to boost tumor suppression. Disclosures No relevant conflicts of interest to declare.

author list (cited authors)

  • Lee, M., Li, J., Fang, S., Zhang, J., Vo, A., Han, W., ... Huang, Y.

citation count

  • 0

publication date

  • November 2020

published in