Context-Dependent Modulation of Macrophage Plasticity by Cordycepin Drives Tumor Regression in Melanoma

BACKGROUND AND AIM: cultivar, validate its systemic anti-tumor efficacy, and elucidate the mechanobiological cues regulating CDC-driven macrophage functions under varying cell-density states. EXPERIMENTAL PROCEDURE: intratumoral adoptive transfer in B16F10 tumor-bearing mice. KEY RESULTS: . CONCLUSIONS AND IMPLICATIONS: CDC modulates macrophage activation through a unique mechanobiological switch. Under high-density conditions-mimicking the dense tumor microenvironment-CDC enhances A2AR-mediated NF-κB activation, boosting macrophage activation, recruitment, and phagocytosis to facilitate tumor regression. These findings establish CDC as a context-dependent immunomodulator capable of reprogramming macrophages toward a tumoricidal phenotype.