Natural killer (NK) cells, classically known for their cytotoxic activity against tumors, are increasingly recognized for their immunoregulatory roles. Recent evidence suggests that they may act as immunotherapeutic enhancers by modulating the dendritic cell (DC)–T cell axis. In this study, we investigated whether secretomes from chemically primed NK cells can potentiate adaptive antitumor immunity via DC reprogramming. Conditioned media (CM) were collected from activated NK cells and applied to immature DCs. The CM-treated DCs exhibited enhanced tumor-homing abilities without affecting non-specific migration toward FBS. These DCs also showed increased production of pro-inflammatory cytokines (IL-6, IL-12p70, TNF-α) and heightened responsiveness to TLR7/8 agonists, suggesting a sensitized and immunogenic profile.
To evaluate in vivo effects, CM from activated NK cells were administered to mice in combination with the model antigen ovalbumin (OVA). Subsequent analysis revealed increased infiltration of SIINFEKL-presenting DCs and CD8⁺ T cells expressing activation markers (CD25, IFN-γ) in lymphoid organs. Furthermore, mice receiving CM exhibited delayed tumor onset in a B16-OVA melanoma model.
These findings indicate that activated NK cells can imprint tumor-specific migratory and functional traits on DCs, thereby establishing a reprogramming axis with promising therapeutic potential in cancer immunotherapy.