带电底物处理增强 T 细胞介导的癌症免疫治疗

Biophysical cues play a crucial role in T cell biology, yet their implications in adoptive T cell therapy (ACT) remain largely unknown.

Here, we investigate the effect of electrical stimuli on CD8 + T cells using a charged substrate composed of electroactive nanocomposites with tunable surface charge intensities. Electrical stimuli enhance the persistence and tumor-suppressive efficacy of transferred T cells, with effects dependent on substrate charge.

Single-cell RNA-sequencing analysis unveils a decrease in virtual memory T (Tvm) cells and an increase in proliferative potential T (Tpp) cells, which exhibit superior antitumor activity and metabolic adaptations relative to those treated with uncharged substrate. ATAC-seq profiling demonstrates heightened accessibility at upstream binding sites for EGR1, a transcription factor critical for Tpp cell differentiation.

Mechanistically, the charged substrate disrupts ionic TCR-lipid interactions, amplifies TCR signaling, and activates EGR1, thereby impeding Tvm polarization during ex vivo culture.

Our findings thus highlight the importance of extracellular electrical stimuli in shaping T cell fate, offering potential for optimizing ACT for therapeutic applications.