TY - JOUR
T1 - Type 2 innate lymphoid cells impede IL-33-mediated tumor suppression
AU - Long, Alan
AU - Dominguez, Donye
AU - Qin, Lei
AU - Chen, Siqi
AU - Fan, Jie
AU - Zhang, Minghui
AU - Fang, Deyu
AU - Zhang, Yi
AU - Kuzel, Timothy M.
AU - Zhang, Bin
N1 - Funding Information:
This work was supported in part by National Institutes of Health Grants CA149669, CA208354, and CA222963, the Melanoma Research Alliance Pilot Award, the Northwestern University Robert H. Lurie Comprehensive Cancer Center Flow Cytometry Facility, a Cancer Center Support grant (NCI CA060553), and the Walter S. and Lucienne Driskill Immunotherapy Research fund.
Publisher Copyright:
Copyright © 2018 by The American Association of Immunologists, Inc.
PY - 2018/12/1
Y1 - 2018/12/1
N2 - 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.
AB - 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.
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U2 - 10.4049/jimmunol.1800173
DO - 10.4049/jimmunol.1800173
M3 - Article
C2 - 30373846
AN - SCOPUS:85056706549
VL - 201
SP - 3456
EP - 3464
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 11
ER -