Type 2 innate lymphoid cells impede IL-33-mediated tumor suppression

Alan Long, Donye Dominguez, Lei Qin, Siqi Chen, Jie Fan, Minghui Zhang, Deyu Fang, Yi Zhang, Timothy Michael Kuzel, Bin Zhang*

*Corresponding author for this work

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

Although a number of studies have recently explored the contribution of the adaptive immunity in IL-33-mediated antitumor effects, innate immune involvement has been poorly characterized. Utilizing Rag12/2 mice (lacking T and B lymphocytes), we show in this study that either systemic administration of recombinant IL-33 or ectopic expression of IL-33 in melanoma cells is sufficient to inhibit tumor growth independent of adaptive antitumor immunity. We have demonstrated that IL-33-mediated antitumor effects depend on expansion and activation of NK cells. Interestingly, IL-33 also promoted the expansion of active type 2 innate lymphoid cells (ILC2s) via its receptor, ST2, which in turn inhibited NK activation and cytotoxicity. This IL-33-induced ILC2 activity coincided with greater expression of the immunosuppressive ectoenzyme CD73. Removal of CD73 from ILC2s in culture with NK cells resulted in markedly increased activation levels in NK cells, offering a potential mechanism by which ILC2s might suppress NK cell-mediated tumor killing. Thus, our data reveal an important contribution of IL-33-induced ILC2 to tumor growth by weakening NK cell activation and tumor killing, regardless of adaptive immunity.

Original languageEnglish (US)
Pages (from-to)3456-3464
Number of pages9
JournalJournal of Immunology
Volume201
Issue number11
DOIs
StatePublished - Dec 1 2018

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Long, A., Dominguez, D., Qin, L., Chen, S., Fan, J., Zhang, M., Fang, D., Zhang, Y., Kuzel, T. M., & Zhang, B. (2018). Type 2 innate lymphoid cells impede IL-33-mediated tumor suppression. Journal of Immunology, 201(11), 3456-3464. https://doi.org/10.4049/jimmunol.1800173