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

• Published in: Blood Vol. 136; no. Supplement 1; p. 27
• Main Authors: Lee, Minjung, Li, Jianfang, Fang, Shaohai, Zhang, Joanna, Vo, Anh Tran Tram, Han, Wei, Zeng, Hongxiang, Isgandarova, Sevinj, Moczygemba, Margarita Martinez, Zhou, Yubin, Li, Jia, Sun, Deqiang, Huang, Yun
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 05.11.2020
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2020-137242

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. No relevant conflicts of interest to declare.