CSF3 and neoplasm: Additionally, neutrophils release IL-12, crucial for NK cells’ enhanced IFNγ and perforin production.417 However, in tumor-bearing animals, neutrophils downregulated chemokine receptor CCR1, NKp46, and NKG2D expression in NK cells through direct contact with NK cells, weakening their tumor infiltration and responsiveness.418 This immunosuppression was mediated by neutrophils’ increased PD-L1 expression, induced by G-CSF, the regulator of neutrophils’ generation and differentiation, and the STAT3 signaling.