Details

Autor(en) / Beteiligte

• TERME, Magali
• ULLRICH, Evelyn
• PREVOST-BLONDEL, Armelle
• KATO, Masashi
• SCHULTZE, Joachim L
• TARTOUR, Eric
• KROEMER, Guido
• CHAPUT, Nathalie
• ZITVOGEL, Laurence
• AYMERIC, Laetitia
• MEINHARDT, Kathrin
• DESBOIS, Mélanie
• DELAHAYE, Nicolas
• VIAUD, Sophie
• RYFFEL, Bernard
• YAGITA, Hideo
• KAPLANSKI, Gilles

Titel

IL-18 Induces PD-1: Dependent Immunosuppression in Cancer

Ist Teil von

• Cancer research (Chicago, Ill.), 2011-08, Vol.71 (16), p.5393-5399

Ort / Verlag

Philadelphia, PA: American Association for Cancer Research

Erscheinungsjahr

2011

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.