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

Yulong Gao Fernando Souza-Fonseca-Guimaraes Tobias Bald Susanna S. Ng Arabella Young Shin Foong Ngiow Jai Rautela 1, 2 Jasmin Straube Nic Waddell Stephen J. Blake Juming Yan Laurent Bartholin 3 Jason S. Lee Eric Vivier 4 Kazuyoshi Takeda Meriem Messaoudene 5, 6 Laurence Zitvogel- Michele W. L. Teng Gabrielle T. Belz Christian R. Engwerda Nicholas D. Huntington 1, 2 Kyohei Nakamura Michael Hoelzel Mark J. Smyth
1 The Walter & Eliza Hall Institute of Medical Research
2 University of Melbourne
3 UNICANCER/CRCL - Centre de Recherche en Cancérologie de Lyon
4 CIML - Centre d'Immunologie de Marseille - Luminy
5 IUH - Institut Universitaire d'Hématologie
6 A2T - Alloimmunité-Autoimmunité-Transplantation
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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https://hal-amu.archives-ouvertes.fr/hal-01765092
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Submitted on : Thursday, April 12, 2018 - 3:38:45 PM
Last modification on : Monday, June 14, 2021 - 1:58:05 PM

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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, Nature Publishing Group, 2017, 18 (9), pp.1004+. ⟨10.1038/ni.3800⟩. ⟨hal-01765092⟩

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