During cancer development, a number of regulatory cell subsets and immunosuppressive cytokines subvert adaptive immune responses. Although it has been shown that tumor-derived interleukin (IL)-18 participates in the PD-1-dependent tumor progression in NK cell-controlled cancers, the mechanistic cues underlying this immunosuppression remain unknown. Here, we show that IL-18 converts a subset of Kit - (CD11b -) into Kit +natural killer (NK) cells, which accumulate in all lymphoid organs of tumor bearers and mediate immunoablative functions. Kit + NK cells overexpressed B7-H1/PD-L1, a ligand for PD-1. The adoptive transfer of Kit + NK cells promoted tumor growth in two pulmonary metastases tumor models and significantly reduced the dendritic and NK cell pools residing in lymphoid organs in a B7-H1-dependent manner. Neutralization of IL-18 by RNA interference in tumors or systemically by IL-18-binding protein dramatically reduced the accumulation of Kit +CD11b - NK cells in tumor bearers. Together, our findings show that IL-18 produced by tumor cells elicits Kit +CD11b - NK cells endowed with B7-H1-dependent immunoablative functions in mice.
ASJC Scopus subject areas
- Cancer Research