Thermal potentiation improves IFN-γ production but not cytotoxicity in human CAR-T cells

Abstract

Abstract Objective Body temperature plays an important role in cancer, with febrile temperature generally associated with improved cancer resistance. In murine models, this resistance has been linked to the cytotoxic T cells, whose differentiation into cancer-killing effector cells is poor at lower but robust at elevated temperatures. If conserved, temperature-mediated potentiation of patient-derived T cells could be implemented to improve the existing cancer treatments, including the chimeric antigen receptor T-cell therapy (CAR T-cell therapy). Here, we tested this possibility using human STEAP1 CAR-T cells developed to target prostate cancer. Results In mice, transient exposure to febrile temperature (39–40 ºC) increases the production of IFN-γ and the cancer-killing ability of CD8 + T cells. Using a similar temperature treatment, we observed elevated levels of IFN-γ also in the human CAR-T cells. However, these cells displayed no improvement in their ability to kill cancer cells. Although we cannot discount the possibility that alternative protocols might lead to other outcomes, our findings suggest that incorporating thermal potentiation into existing protocols of CAR-T cell therapy may be more complicated than anticipated.

Keywords

• CAR-T
• STEAP1
• CD8 + T cells
• IFN-γ
• Cancer immunotherapy
• Hyperthermia