Proteotoxic Stress and Protein Misfolding Drive T Cell Exhaustion and Immune Evasion
The study reveals that proteotoxic stress response (PSR) drives T cell exhaustion in cancer, characterized by increased protein synthesis, chaperone activation, and protein aggregation, with sustained AKT activity as a key upstream driver. Targeting specific chaperones like gp96 and BiP can mitigate exhaustion and improve immunotherapy outcomes.