Cancer-induced immunosuppression: IL-18-elicited immunoablative NK cells

Magali Terme, Evelyn Ullrich, Laetitia Aymeric, Kathrin Meinhardt, Jérôme D. Coudert, Mélanie Desbois, François Ghiringhelli, Sophie Viaud, Bernard Ryffel, Hideo Yagita, Lieping Chen, Salaheddine Mécheri, Gilles Kaplanski, Armelle Prévost-Blondel, Masashi Kato, Joachim L. Schultze, Eric Tartour, Guido Kroemer, Mariapia Degli-Esposti, Nathalie ChaputLaurence Zitvogel

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2757-2767
Number of pages11
JournalCancer Research
Volume72
Issue number11
DOIs
StatePublished - Jun 1 2012

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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