TET2 regulates early and late transitions in exhausted CD8⁺ T cell differentiation and limits CAR T cell function.

ABSTRACT: CD8⁺ T cell exhaustion hampers control of cancer and chronic infections and limits chimeric antigen receptor (CAR) T cell efficacy. Targeting TET2 in CAR T cells provides therapeutic benefit; however, TET2's role in exhausted T cell (T_EX) development is unclear. In chronic lymphocytic choriomeningitis virus (LCMV) infection, TET2 drove conversion from stem cell-like T_EX progenitors toward terminally differentiated and effector (T_EFF)-like T_EX. TET2 also enforced a terminally differentiated state in the early bifurcation between T_EFF and T_EX, indicating broad roles for TET2 in acquisition of effector biology. To exploit the therapeutic potential of TET2, we developed clinically actionable TET2-targete

SUBMITTER: Dimitri AJ 

PROVIDER: S-EPMC11559603 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature