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CD38-NADAxis Regulates Immunotherapeutic Anti-Tumor T Cell Response.

Cell Metab.. 2018; 
Chatterjee Shilpak,Daenthanasanmak Anusara,Chakraborty Paramita,Wyatt Megan W,Dhar Payal,Selvam Shanmugam Panneer,Fu Jianing,Zhang Jinyu,Nguyen Hung,Kang Inhong,Toth Kyle,Al-Homrani Mazen,Husain Mahvash,Beeson Gyda,Ball Lauren,Helke Kristi,Husain Shahid,Garrett-Mayer Elizabeth,Hardiman Gary,Mehrotra Meenal,Nishimura Michael I,Beeson Craig C,Bupp Melanie Gubbels,Wu Jennifer,Ogretmen Besim,Paulos Chrystal M,Rathmell Jeffery,Yu Xue-Zhong,Mehrotra Shi
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Heightened effector function and prolonged persistence, the key attributes of Th1 and Th17 cells, respectively, are key features of potent anti-tumor T?cells. Here, we established ex?vivo culture conditions to generate hybrid Th1/17 cells, which persisted long-term in?vivo while maintaining their effector function. Using transcriptomics and metabolic profiling approaches, we showed that the enhanced anti-tumor property of Th1/17 cells was dependent on the increased NAD-dependent activity of the histone deacetylase Sirt1. Pharmacological or genetic inhibition of Sirt1 activity impaired the anti-tumor potential of Th1/17 cells. Importantly, T?cells with reduced surface expression of the NADase CD38 ... More