Michael St Paul, Samuel D Saibil, Meghan Kates, SeongJun Han, Scott C Lien, Rob C Laister, Kebria Hezaveh, Andreas Kloetgen, Susanne Penny, Tingxi Guo, Carlos Garcia-Batres, Logan K Smith, Douglas C Chung, Alisha R Elford, Azin Sayad, Devanand Pinto, Tak W Mak, Naoto Hirano, Tracy McGaha, Pamela S Ohashi
The manipulation of T cell metabolism to enhance anti-tumor activity is an area of active investigation. Here, we report that activating the amino acid starvation response in effector CD8+ T cells ex vivo using the general control non-depressible 2 (GCN2) agonist halofuginone (halo) enhances oxidative metabolism and effector function. Mechanistically, we identified autophagy coupled with the CD98-mTOR axis as key downstream mediators of the phenotype induced by halo treatment. The adoptive transfer of halo-treated CD8+ T cells into tumor-bearing mice led to robust tumor control and curative responses...
March 1, 2024: Cell reports medicine