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Journal Articles Nature Immunology Year : 2017

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

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Yulong Gao
  • Function : Author
Tobias Bald
  • Function : Author
Susanna S. Ng
  • Function : Author
Arabella Young
  • Function : Author
Shin Foong Ngiow
  • Function : Author
Jasmin Straube
  • Function : Author
Nic Waddell
  • Function : Author
Stephen J. Blake
  • Function : Author
Juming Yan
  • Function : Author
Jason S. Lee
  • Function : Author
Eric Vivier
Kazuyoshi Takeda
  • Function : Author
Laurence Zitvogel-
  • Function : Author
Michele W. L. Teng
  • Function : Author
Gabrielle T. Belz
  • Function : Author
Christian R. Engwerda
  • Function : Author
Kyohei Nakamura
  • Function : Author
Michael Hoelzel
  • Function : Author
Mark J. Smyth
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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-beta-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(-)Eomes(int)) 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-beta-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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Dates and versions

hal-01765092 , version 1 (12-04-2018)

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Yulong Gao, Fernando Souza-Fonseca-Guimaraes, Tobias Bald, Susanna S. Ng, Arabella Young, et al.. Tumor immunoevasion by the conversion of effector NK cells into type 1 innate lymphoid cells. Nature Immunology, 2017, 18 (9), pp.1004+. ⟨10.1038/ni.3800⟩. ⟨hal-01765092⟩
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