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0The paper details the development of a dual-compartment lipid carrier system designed to overcome the immunosuppressive effects of lactate in solid tumors. By engineering natural killer (NK) cells to carry nicotinamide mononucleotide (NMN) and dichloroacetate (DCA), researchers successfully restored intracellular NAD+ levels and depleted extracellular lactate. This innovative approach "hijacks" the ER-Golgi secretory pathway, allowing for the precise, localized release of therapeutic payloads at the tumor site. Experimental results in osteosarcoma models and patient-derived xenografts demonstrate that this spatiotemporal metabolic reprogramming significantly enhances immune cell persistence and tumor suppression. Furthermore, the study suggests this exocytosis-co-option strategy is a versatile platform that can be adapted to improve the efficacy of T cell and macrophage therapies. Overall, the work establishes a new method for empowering cellular immunotherapies against metabolically hostile cancer environments without inducing systemic toxicity.
References:
Chen S, Shao Z, Zhou Y, et al. Dual compartment lipid carriers hijack exocytosis to empower natural killer cells against solid tumours[J]. Nature Communications, 2026.
