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To break through this bottleneck, a combined intervention strategy has emerged: Shikonin (SHK) and curcumin (CUR) form a self-delivering nanosystem (chitosan-polyethylene glycol nanoparticles, CS-PEG NPs) that synergistically induces endoplasmic reticulum stress and Ca 2+ homeostasis imbalance, which significantly increases the release of DAMPs, thereby increasing DC maturation and significantly increasing the infiltration density of CTLs in the core region of the tumor (from 5% to 20%) (211), Thus reversing the immunosuppression mediated by regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs)

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This activation disrupts insulin signaling and promotes glucose production in the liver

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