Fig. 3

The CAR structures, activation signaling and epigenetic regulators independently or collaboratively participate in CAR T cells differentiation and/or exhaustion. The differences in CAR structures (Extracellular structures, transmembrane and intracellular domains, the accessory structures), CAR signaling and TCR engagement lead to differences in activation strength and duration, as well the activation pathways, which further influence the expression or activities of differentiation and/or exhaustion-associated transcription factors and epigenetic regulators, and ultimately CAR T cells manifest as various degrees of differentiation and/or exhaustion during ex vivo expansion or following in vivo antigen exposure. Thereby, cell differentiation and exhaustion which may lies at the central link in determining CAR T cells in vivo persistence, can be modulated by intervention of the above influence factors