Oct 31, 2018

Type 2 Innate Lymphoid Cells Impede IL-33-Mediated Tumor Suppression

The Journal of Immunology : Official Journal of the American Association of Immunologists
Alan LongBin Zhang

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 Rag1-/- 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.

Mentioned in this Paper

Study
RAG1 gene
Cacna1b protein, mouse
NK Cell Activation
Lymphoid Cells
Neoplasms
Administration Procedure
Cell Proliferation
Lymphocyte Activation
B-Lymphocytes

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