Post-traumatic stress disorder impairs CD8+ T cell-dependent anti-tumor immune responses by downregulating thiamine.

Post-traumatic stress disorder (PTSD) is a severe and chronic psychiatric condition. However, whether PTSD influences tumor immunity remains poorly understood. In this study, we demonstrated that PTSD promotes the growth of subcutaneous transplant tumors in mice, an effect that can be reversed by anti-CD8 antibody treatment. Furthermore, we found that PTSD downregulates serum thiamine levels, which mediates the tumor-promoting effects observed in PTSD mice. In vitro, thiamine enhances CD8+ T cell activation and cytotoxic function. Mechanistically, thiamine augments tricarboxylic acid (TCA) cycle flux, thereby improving mitochondrial function and energy production, which in turn enhances the anti-tumor activity of CD8+ T cells. Clinical data corroborated these findings, showing that thiamine supplementation promotes the activation, cytotoxic function, and mitochondrial fitness of peripheral blood mononuclear cell (PBMC)-derived CD8+ T cells. Our findings highlight the critical role of PTSD-induced thiamine deficiency in impairing tumor-infiltrating CD8+ T cell function. These results suggest that thiamine supplementation may represent a potential therapeutic strategy to mitigate cancer risk and progression in PTSD patients.