Lack of p53 Augments Antitumor Functions in Cytolytic T Cells.

摘要: Repetitive stimulation of T-cell receptor (TCR) with cognate antigen results in robust proliferation and expansion the T cells, also imprints them replicative senescence signatures. Our previous studies have shown that life-span antitumor function cells can be enhanced by inhibiting reactive oxygen species (ROS) or intervening ROS-dependent JNK activation leads to its activation-induced cell death. Because tumor suppressor protein p53 is a redox active transcription factor regulates cellular ROS generation triggers downstream factor-mediating apoptosis, we determined if levels could influence persistence tumor-reactive cells. Using h3T TCR transgenic mice, human tyrosinase epitope-reactive developed on knockout (KO) background, role regulating function. data show as compared h3T-p53 KO exhibited glycolytic commitment correlated increased proliferation, IFNγ secretion, cytolytic capacity, expression stemness gene signature, decreased TGF-β signaling. This effector improved control subcutaneously established murine melanoma after adoptive transfer p53-KO Pharmacological inhibition TCR-transduced using combination inhibitors potentiated persistence. Thus, our highlight key response targeting this pathway potential translational significance therapy. Cancer Res; 76(18); 5229-40. ©2016 AACR.