BACH2 overexpression

Interestingly, both CD28 and CD40LG were indispensable for T-ALL survival, since largely or completely silencing CD28 and CD40LG led to rapid cell death, whereas partial knockdown of them resulted in cell-cycle arrest and enhanced apoptosis. More importantly, BACH2-mediated CD28 and CD40LG signals contributed to cell migration and dissemination of T-ALL cells to the bone marrow, thus adding a new layer to the BACH2-mediated tumor immunoregulation in T-cell malignancies.

Phenotypic analysis revealed at time of cell failure revealed that almost all 22/28+_BACH2 cells expressed markers of a central memory phenotype (CD62LhiCD45ROhi). Collectively, these data suggest that BACH2 overexpression can overcome tonic CAR signaling-induced dysfunction by antagonizing exhaustion programs but simultaneously "locks" these cells into a memory state with restrained effector function, thus limiting their long-term efficacy.