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Nat Immunol. 2017 Sep;18(9):1004-1015. doi: 10.1038/ni.3800. Epub 2017 Jul 31.

Tumor immunoevasion by the conversion of effector NK cells into type 1 innate lymphoid cells.

Author information

1
Immunology in Cancer and Infection, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia.
2
School of Medicine, The University of Queensland, Herston, Queensland, Australia.
3
Molecular Immunology Division, The Walter and Eliza Hall Institute of Medical Research, Department of Medical Biology and The University of Melbourne, Parkville, Victoria, Australia.
4
Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Melbourne, Victoria, Australia.
5
Immunology and Infection, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia.
6
School of Natural Sciences, Griffith University, Nathan, Queensland, Australia.
7
Medical Genomics, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia.
8
Cancer Immunoregulation and Immunotherapy, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia.
9
Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Centre de recherche en cancérologie de Lyon, Lyon, France.
10
Control of Gene Expression Laboratory, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia.
11
Centre d'Immunologie de Marseille-Luminy, Aix Marseille Université, INSERM, CNRS, Marseille, France.
12
Division of Cell Biology, Biomedical Research Center and Department of Biofunctional Microbiota, Graduate School of Medicine, Juntendo University, Bunkyo-ku, Tokyo, Japan.
13
INSERM U1015, Gustave Roussy Cancer Campus, Villejuif, France.
14
Gustave Roussy Cancer Campus, Villejuif, France.
15
University Paris-Saclay, Kremlin Bicêtre, Paris, France.
16
CIC1428, Gustave Roussy Cancer Campus, Villejuif, France.
17
Unit for RNA Biology, Department of Clinical Chemistry and Clinical Pharmacology, University of Bonn, Bonn, Germany.

Abstract

Avoiding destruction by immune cells is a hallmark of cancer, yet how tumors ultimately evade control by natural killer (NK) cells remains incompletely defined. Using global transcriptomic and flow-cytometry analyses and genetically engineered mouse models, we identified the cytokine-TGF-β-signaling-dependent conversion of NK cells (CD49a-CD49b+Eomes+) into intermediate type 1 innate lymphoid cell (intILC1) (CD49a+CD49b+Eomes+) populations and ILC1 (CD49a+CD49b-Eomesint) populations in the tumor microenvironment. Strikingly, intILC1s and ILC1s were unable to control local tumor growth and metastasis, whereas NK cells favored tumor immunosurveillance. Experiments with an antibody that neutralizes the cytokine TNF suggested that escape from the innate immune system was partially mediated by TNF-producing ILC1s. Our findings provide new insight into the plasticity of group 1 ILCs in the tumor microenvironment and suggest that the TGF-β-driven conversion of NK cells into ILC1s is a previously unknown mechanism by which tumors escape surveillance by the innate immune system.

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PMID:
28759001
DOI:
10.1038/ni.3800
[Indexed for MEDLINE]

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