Conclusion
These data suggest that spermidine treatment presents an opportunity to improve the antitumor effect of TCR-Ts for the treatment of solid tumors.
Methods
We first evaluated autophagy level of senescent TCR-Ts, and then the senescent TCR-Ts were expanded in vitro for 7 days with and without spermidine treatment, respectively. Furthermore, the proliferative potential, phenotypical characteristics and functionality of the propagated senescent TCR-Ts were analysed in vitro and in vivo after 7-day ex vivo expansion.
Results
We found that autophagic flux of senescent TCR-T cells was significantly impaired. The restoration of autophagic flux via spermidine treatment reduced the expression of inhibitory immunoreceptors (PD-1, TIM-3 or LAG-3), enhanced proliferation and effector functions and subsequently demonstrated the superior in vitro and in vivo antitumor activity of TCR-Ts.