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Notably, translational delivery is optimized by ex vivo pretreatment during CAR-T cell manufacturing (2-day exposure during activation) rather than systemic administration: in vivo pentanoate fails to enhance anti-PD-1 therapy, whereas ex vivo programming preserves its metabolic-epigenetic effects and avoids off-target immunosuppression (e.g., Treg induction, which is triggered by butyrate but not pentanoate) (108, 109)

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