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 |
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Pages (de - à) | 1004-1015 |
Nombre de pages | 12 |
journal | Nature Immunology |
Volume | 18 |
Numéro de publication | 9 |
Les DOIs | |
état | Publié - 22 août 2017 |
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Dans: Nature Immunology, Vol 18, Numéro 9, 22.08.2017, p. 1004-1015.
Résultats de recherche: Contribution à un journal › Article › Revue par des pairs
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.
UR - http://www.scopus.com/inward/record.url?scp=85027867260&partnerID=8YFLogxK
U2 - 10.1038/ni.3800
DO - 10.1038/ni.3800
M3 - Article
C2 - 28759001
AN - SCOPUS:85027867260
SN - 1529-2908
VL - 18
SP - 1004
EP - 1015
JO - Nature Immunology
JF - Nature Immunology
IS - 9
ER -