Target-induced proximity labelling allows us to isolate the first-division proximal-daughter and distal-daughter CD8 CARTs, revealing how their differentiation impacts their functional fates.
Proximal daughters inherit surface proteins resembling activated CARTs while distal daughters express a resting phenotype; this asymmetry in division shapes their metabolic and cytolytic capacities.
Despite having a memory-like profile, distal daughters exhibit transient potent cytolytic activity akin to proximal daughters, illustrating a novel effector-like state.
Asymmetric cell division highlights essential mechanisms behind CART differentiation, with implications for enhancing the efficacy of CAR T-cell therapies.
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