| First Author | Terme M | Year | 2012 |
| Journal | Cancer Res | Volume | 72 |
| Issue | 11 | Pages | 2757-67 |
| PubMed ID | 22427351 | Mgi Jnum | J:189351 |
| Mgi Id | MGI:5445078 | Doi | 10.1158/0008-5472.CAN-11-3379 |
| Citation | Terme M, et al. (2012) Cancer-induced immunosuppression: IL-18-elicited immunoablative NK cells. Cancer Res 72(11):2757-67 |
| abstractText | 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. |
