Tet2 Inactivation Enhances the Antitumor Activity of Tumor-Infiltrating Lymphocytes.

ABSTRACT: Inactivation of tumor-infiltrating lymphocytes (TIL) is one of the mechanisms mitigating antitumor 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 antitumor activity of TILs with an efficacy comparable to immune checkpoint inhibition imposed by anti-PD-L1 treatment. Single-cell RNA-sequencing analysis suggested that Tet2-deficient TILs exhibit effector-like features. Transcriptomic and ATAC-sequencing analysis showed that Tet2 ablation reshapes chromatin accessibility and favors binding of transcription factors geared toward CD8⁺ T-cell activati

SUBMITTER: Lee M 

PROVIDER: S-EPMC8137576 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature