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; Jasmin Straube; Nic Waddell; Stephen J. Blake; Juming Yan; Laurent Bartholin; Jason S. Lee; Eric Vivier; Kazuyoshi Takeda; Meriem Messaoudene; Laurence Zitvogel; Michele W.L. Teng; Gabrielle T. Belz; Christian R. Engwerda; Nicholas D. Huntington; Kyohei Nakamura; Michael Hölzel; Mark J. Smyth

doi:10.1038/ni.3800

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, Jasmin Straube, Nic Waddell, Stephen J. Blake, Juming Yan, Laurent Bartholin, Jason S. Lee, Eric Vivier, Kazuyoshi Takeda, Meriem Messaoudene, Laurence Zitvogel, Michele W.L. Teng, Gabrielle T. Belz, Christian R. EngwerdaNicholas D. Huntington, Kyohei Nakamura, Michael Hölzel, Mark J. Smyth

Résultats de recherche: Contribution à un journal › Article › Revue par des pairs

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Résumé

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-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-β-driven conversion of NK cells into ILC1s is a previously unknown mechanism by which tumors escape surveillance by the innate immune system.

langue originale	Anglais
Pages (de - à)	1004-1015
Nombre de pages	12
journal	Nature Immunology
Volume	18
Numéro de publication	9
Les DOIs	https://doi.org/10.1038/ni.3800
état	Publié - 22 août 2017

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10.1038/ni.3800

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Gao, Y., Souza-Fonseca-Guimaraes, F., Bald, T., Ng, S. S., Young, A., Ngiow, S. F., Rautela, J., Straube, J., Waddell, N., Blake, S. J., Yan, J., Bartholin, L., Lee, J. S., Vivier, E., Takeda, K., Messaoudene, M., Zitvogel, L., Teng, M. W. L., Belz, G. T., ... Smyth, M. J. (2017). Tumor immunoevasion by the conversion of effector NK cells into type 1 innate lymphoid cells. Nature Immunology, 18(9), 1004-1015. https://doi.org/10.1038/ni.3800

@article{31249ed2cc544525ac6e976d07005e7f,

title = "Tumor immunoevasion by the conversion of effector NK cells into type 1 innate lymphoid cells",

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-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-β-driven conversion of NK cells into ILC1s is a previously unknown mechanism by which tumors escape surveillance by the innate immune system.",

author = "Yulong Gao and Fernando Souza-Fonseca-Guimaraes and Tobias Bald and Ng, {Susanna S.} and Arabella Young and Ngiow, {Shin Foong} and Jai Rautela and Jasmin Straube and Nic Waddell and Blake, {Stephen J.} and Juming Yan and Laurent Bartholin and Lee, {Jason S.} and Eric Vivier and Kazuyoshi Takeda and Meriem Messaoudene and Laurence Zitvogel and Teng, {Michele W.L.} and Belz, {Gabrielle T.} and Engwerda, {Christian R.} and Huntington, {Nicholas D.} and Kyohei Nakamura and Michael H{\"o}lzel and Smyth, {Mark J.}",

note = "Funding Information: We thank R. Schreiber (Washington University School of Medicine) for MCA1956 fibrosarcoma cells and anti-IFN-γ and anti-TNF hybridomas; the animal house and flow cytometry facilities at QIMR Berghofer Medical Research Institute and Walter and Eliza Hall Institute of Medical Research; E. Loza, K. Elder, L. Town, L. Spencer, T. Camilleri and T. Kratina, for mouse breeding, maintenance and genotyping; and K. MacDonald, D. Smith, A. Kallies, L. Beattie, R. Allan, G. Hill and S. Nutt for discussion, comments and advice on this project. Supported by the National Health and Medical Research Council of Australia (Senior Principal Research Fellowship 1078671 to M.J.S.; Peter Doherty Early Career Fellowship 1088703 to F.S.-F.-G. and 1124690 to T.B.; project grant 1027472 to G.T.B.; Elizabeth Blackburn NHMRC Fellowship to G.T.B.; Independent Research Institute Infrastructure Support scheme grant to G.T.B.; project grants 1066770 & 1057852 N.D.H.; and RD Wright Career development Fellowship 1112113 to N.W.), the Cancer Research Institute Clinical and Laboratory Integration Programs (M.J.S. and N.D.H.), Queensland Institute of Medical Research Berghofer International PhD Scholarship (Y.G. and J.Y.), University of Queensland International Scholarship (Y.G. and J.Y.), the National Breast Cancer Foundation (PF-15-008 to F.S.-F.-G.), Cure Cancer Australia (Priority-Driven Young Investigator Project Grant 1082709 and 1120725 to F.S.-F.-G.), European Molecular Biology Organization (long-term fellowship ALTF 945-2015 to T.B.), the Naito Foundation (K.N.), Cancer Council Queensland (PhD fellowship to A.Y.), Griffith University (PhD scholarships to S.S.N.), Inserm-Avenir-Grant (L.B.), Ligue Nationale Contre le Cancer (L.B.), Fondation ARC Pour la Recherche sur le Cancer (L.B.), the Victorian State Government Operational Infrastructure Scheme (G.T.B.), the Harry J Lloyd Charitable Trust (Melanoma Research Grant to N.D.H.) and the DFG Excellence Cluster Immunosensation (EXC 1023 to M.H.).",

year = "2017",

month = aug,

day = "22",

doi = "10.1038/ni.3800",

language = "English",

volume = "18",

pages = "1004--1015",

journal = "Nature Immunology",

issn = "1529-2908",

number = "9",

}

Gao, Y, Souza-Fonseca-Guimaraes, F, Bald, T, Ng, SS, Young, A, Ngiow, SF, Rautela, J, Straube, J, Waddell, N, Blake, SJ, Yan, J, Bartholin, L, Lee, JS, Vivier, E, Takeda, K, Messaoudene, M, Zitvogel, L, Teng, MWL, Belz, GT, Engwerda, CR, Huntington, ND, Nakamura, K, Hölzel, M & Smyth, MJ 2017, 'Tumor immunoevasion by the conversion of effector NK cells into type 1 innate lymphoid cells', Nature Immunology, VOL. 18, Numéro 9, p. 1004-1015. https://doi.org/10.1038/ni.3800

TY - JOUR

T1 - Tumor immunoevasion by the conversion of effector NK cells into type 1 innate lymphoid cells

AU - Gao, Yulong

AU - Souza-Fonseca-Guimaraes, Fernando

AU - Bald, Tobias

AU - Ng, Susanna S.

AU - Young, Arabella

AU - Ngiow, Shin Foong

AU - Rautela, Jai

AU - Straube, Jasmin

AU - Waddell, Nic

AU - Blake, Stephen J.

AU - Yan, Juming

AU - Bartholin, Laurent

AU - Lee, Jason S.

AU - Vivier, Eric

AU - Takeda, Kazuyoshi

AU - Messaoudene, Meriem

AU - Zitvogel, Laurence

AU - Teng, Michele W.L.

AU - Belz, Gabrielle T.

AU - Engwerda, Christian R.

AU - Huntington, Nicholas D.

AU - Nakamura, Kyohei

AU - Hölzel, Michael

AU - Smyth, Mark J.

N1 - Funding Information: We thank R. Schreiber (Washington University School of Medicine) for MCA1956 fibrosarcoma cells and anti-IFN-γ and anti-TNF hybridomas; the animal house and flow cytometry facilities at QIMR Berghofer Medical Research Institute and Walter and Eliza Hall Institute of Medical Research; E. Loza, K. Elder, L. Town, L. Spencer, T. Camilleri and T. Kratina, for mouse breeding, maintenance and genotyping; and K. MacDonald, D. Smith, A. Kallies, L. Beattie, R. Allan, G. Hill and S. Nutt for discussion, comments and advice on this project. Supported by the National Health and Medical Research Council of Australia (Senior Principal Research Fellowship 1078671 to M.J.S.; Peter Doherty Early Career Fellowship 1088703 to F.S.-F.-G. and 1124690 to T.B.; project grant 1027472 to G.T.B.; Elizabeth Blackburn NHMRC Fellowship to G.T.B.; Independent Research Institute Infrastructure Support scheme grant to G.T.B.; project grants 1066770 & 1057852 N.D.H.; and RD Wright Career development Fellowship 1112113 to N.W.), the Cancer Research Institute Clinical and Laboratory Integration Programs (M.J.S. and N.D.H.), Queensland Institute of Medical Research Berghofer International PhD Scholarship (Y.G. and J.Y.), University of Queensland International Scholarship (Y.G. and J.Y.), the National Breast Cancer Foundation (PF-15-008 to F.S.-F.-G.), Cure Cancer Australia (Priority-Driven Young Investigator Project Grant 1082709 and 1120725 to F.S.-F.-G.), European Molecular Biology Organization (long-term fellowship ALTF 945-2015 to T.B.), the Naito Foundation (K.N.), Cancer Council Queensland (PhD fellowship to A.Y.), Griffith University (PhD scholarships to S.S.N.), Inserm-Avenir-Grant (L.B.), Ligue Nationale Contre le Cancer (L.B.), Fondation ARC Pour la Recherche sur le Cancer (L.B.), the Victorian State Government Operational Infrastructure Scheme (G.T.B.), the Harry J Lloyd Charitable Trust (Melanoma Research Grant to N.D.H.) and the DFG Excellence Cluster Immunosensation (EXC 1023 to M.H.).

PY - 2017/8/22

Y1 - 2017/8/22

N2 - 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-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-β-driven conversion of NK cells into ILC1s is a previously unknown mechanism by which tumors escape surveillance by the innate immune system.

AB - 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-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-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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DO - 10.1038/ni.3800

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AN - SCOPUS:85027867260

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VL - 18

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EP - 1015

JO - Nature Immunology

JF - Nature Immunology

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