Data from Lack of <i>p53</i> Augments Antitumor Functions in Cytolytic T Cells

• DOI: 10.1158/0008-5472.c.6507755
• Publication Date: 2023-04-01T01:49:33Z
• Authors: Anirban Banerjee; Krishnamurthy Thy...; Shilpak Chatterjee; Paramita Chakraborty; Pravin Kesarwani; Myroslawa Soloshc...; Mazen Al-Hommrani; Kristina Andrijau...; Kelly Moxley; Harinarayanan Jan...; Matthew J. Scheffel; Kristi Helke; Kent Armenson; Viswanathan Palan...; Mark P. Rubinstein; Elizabeth-Garrett...; David J. Cole; Chrystal M. Paulos; Christina Voelkel...; Michael I. Nishimura; Shikhar Mehrotra

&lt;div&gt;Abstract&lt;p&gt;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 &lt;i&gt;p53&lt;/i&gt; 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-&lt;i&gt;p53&lt;/i&gt; 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 &lt;i&gt;p53&lt;/i&gt;-KO Pharmacological inhibition TCR-transduced using combination inhibitors potentiated persistence. Thus, our highlight key response targeting this pathway potential translational significance therapy. &lt;i&gt;Cancer Res; 76(18); 5229–40. ©2016 AACR&lt;/i&gt;.&lt;/p&gt;&lt;/div&gt;