Disruption of TET2 Dioxygenase Enhances Antitumor Efficiency in CD8+ Tumor Infiltrating Lymphocytes

Conclusion: Our novel findings demonstrated the therapeutic potential of Tet2 inactivation in immune cells during cancer immunotherapy. In our study, we observed that Tet2 depleted CD8+ TILs displayed increased anti-tumor efficiency in a mouse model of melanoma. Tet2 deletion could effectively alleviate T cell exhaustion to boost CD8+ TIL function. Nonetheless, since Tet2 deficiency is closely associated with various hematology disorders [6,7]; cautions must be taken to balance the tumor promoting and immune-boosting properties of Tet2 during cancer therapy. A temporally controllable system to inactivate Tet2 in specific immune cells might be most desirable for pursuing future therapeutic intervention by targeting Tet2.References1. Thommen, D. S. & Schumacher, T. N. (2018). Cancer Cell33, 547-562.2. Wherry, E. J. (2011). Nat Immunol12, 492-499.3. Fraietta, J. A., Nobles, C. L., Sammons, M. A.et al. (2018). Nature558, 307-312.4. Pan, W., Zhu, S., Qu, K.et al. (2017). Immunity47, 284-297 e285.5. Mognol, G. P., Spreafico, R., Wong, V.et al. (2017). Proc Natl Acad Sci U S A114, E2776-E2785.6. Couronne, L., Bastard, C. & Bernard, O. A. (2012). N Engl J Med366, 95-96.7. Delhommeau, F., Dupont, S., Della Valle, V.et al. (2009). N Engl J Med360, 2289-2301.DisclosuresNo relevant conflicts of interest to declare.
Source: Blood - Category: Hematology Authors: Tags: 203. Lymphocytes, Lymphocyte Activation, and Immunodeficiency, including HIV and Other Infections: T cell biology Source Type: research