Chemically primed natural killer cells trigger the anti-tumor immune system with their secretomes.

Natural Killer (NK) cells play a crucial role in modulating immune responses by releasing a diverse array of soluble factors, including chemotactic cytokines. Our previous study demonstrated the potent anti-tumor activity of Chem_NK, a term referring to NK cells chemically primed by 25kDa branched polyethyleneimine.

In this study, we observed that the quantity of secreted proteins from Chem_NK significantly surpassed that of control_NK (C_NK) through protein quantification and cytokine membrane array analysis of concentrated NK cell’s secretomes. NK cells educated with Chem_NK's secretome exhibited enhanced migratory capabilities toward target cancer cells in vitro. When C_NK or Chem_NK, both generated from human NK92MI cells, were adoptively transferred into a tumor xenograft model of nude mice, the recipient mice of Chem_NK cell showed a notably higher level of tumor-infiltrating endogenous mouse NK cells. Furthermore, the direct injection of Chem_NK’s secretomes into a lung metastasis model of B16F10 melanoma not only increased intratumoral infiltration of endogenous mouse NK cells, but also substantially inhibited lung metastasis. Our studies revealed that Chem_NK’s secretomes have the activity of potentiating the endogenous anticancer immune system. This study provides new insight into the novel function of Chem_NK cells as an antitumor immune trigger.