| First Author | Terme M | Year | 2011 |
| Journal | Cancer Res | Volume | 71 |
| Issue | 16 | Pages | 5393-9 |
| PubMed ID | 21724589 | Mgi Jnum | J:175445 |
| Mgi Id | MGI:5285754 | Doi | 10.1158/0008-5472.CAN-11-0993 |
| Citation | Terme M, et al. (2011) IL-18 induces PD-1-dependent immunosuppression in cancer. Cancer Res 71(16):5393-9 |
| abstractText | Immunosuppressive cytokines subvert innate and adaptive immune responses during cancer progression. The inflammatory cytokine interleukin-18 (IL-18) is known to accumulate in cancer patients, but its pathophysiological role remains unclear. In this study, we show that low levels of circulating IL-18, either exogenous or tumor derived, act to suppress the NK cell arm of tumor immunosurveillance. IL-18 produced by tumor cells promotes the development of NK-controlled metastases in a PD-1-dependent manner. Accordingly, PD-1 is expressed by activated mature NK cells in lymphoid organs of tumor bearers and is upregulated by IL-18. RNAi-mediated knockdown of IL-18 in tumors, or its systemic depletion by IL-18-binding protein, are sufficient to stimulate NK cell-dependent immunosurveillance in various tumor models. Together, these results define IL-18 as an immunosuppressive cytokine in cancer. Our findings suggest novel clinical implementations of anti-PD-1 antibodies in human malignancies that produce IL-18. |
