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ILC2-driven innate immune checkpoint mechanism antagonizes NK cell antimetastatic function in the lung.
Schuijs, Martijn J; Png, Shaun; Richard, Arianne C; Tsyben, Anastasia; Hamm, Gregory; Stockis, Julie; Garcia, Celine; Pinaud, Silvain; Nicholls, Ashley; Ros, Xavier Romero; Su, Jing; Eldridge, Matthew D; Riedel, Angela; Serrao, Eva M; Rodewald, Hans-Reimer; Mack, Matthias; Shields, Jacqueline D; Cohen, E Suzanne; McKenzie, Andrew N J; Goodwin, Richard J A; Brindle, Kevin M; Marioni, John C; Halim, Timotheus Y F.
Afiliación
  • Schuijs MJ; CRUK Cambridge Institute, University of Cambridge, Cambridge, UK.
  • Png S; CRUK Cambridge Institute, University of Cambridge, Cambridge, UK.
  • Richard AC; CRUK Cambridge Institute, University of Cambridge, Cambridge, UK.
  • Tsyben A; Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK.
  • Hamm G; CRUK Cambridge Institute, University of Cambridge, Cambridge, UK.
  • Stockis J; Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
  • Garcia C; Imaging and Data Analytics, Clinical Pharmacology and Safety Sciences, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK.
  • Pinaud S; CRUK Cambridge Institute, University of Cambridge, Cambridge, UK.
  • Nicholls A; CRUK Cambridge Institute, University of Cambridge, Cambridge, UK.
  • Ros XR; CRUK Cambridge Institute, University of Cambridge, Cambridge, UK.
  • Su J; CRUK Cambridge Institute, University of Cambridge, Cambridge, UK.
  • Eldridge MD; Bioscience Asthma, Research and Early Development, Respiratory & Immunology, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK.
  • Riedel A; CRUK Cambridge Institute, University of Cambridge, Cambridge, UK.
  • Serrao EM; CRUK Cambridge Institute, University of Cambridge, Cambridge, UK.
  • Rodewald HR; MRC Cancer Unit, University of Cambridge, Cambridge, UK.
  • Mack M; CRUK Cambridge Institute, University of Cambridge, Cambridge, UK.
  • Shields JD; Division of Cellular Immunology, German Cancer Research Center, Heidelberg, Germany.
  • Cohen ES; Department of Internal Medicine, University Hospital Regensburg, Regensburg, Germany.
  • McKenzie ANJ; MRC Cancer Unit, University of Cambridge, Cambridge, UK.
  • Goodwin RJA; Bioscience Asthma, Research and Early Development, Respiratory & Immunology, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK.
  • Brindle KM; MRC Laboratory of Molecular Biology, Cambridge, UK.
  • Marioni JC; Imaging and Data Analytics, Clinical Pharmacology and Safety Sciences, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK.
  • Halim TYF; Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
Nat Immunol ; 21(9): 998-1009, 2020 09.
Article en En | MEDLINE | ID: mdl-32747815
Metastasis constitutes the primary cause of cancer-related deaths, with the lung being a commonly affected organ. We found that activation of lung-resident group 2 innate lymphoid cells (ILC2s) orchestrated suppression of natural killer (NK) cell-mediated innate antitumor immunity, leading to increased lung metastases and mortality. Using multiple models of lung metastasis, we show that interleukin (IL)-33-dependent ILC2 activation in the lung is involved centrally in promoting tumor burden. ILC2-driven innate type 2 inflammation is accompanied by profound local suppression of interferon-γ production and cytotoxic function of lung NK cells. ILC2-dependent suppression of NK cells is elaborated via an innate regulatory mechanism, which is reliant on IL-5-induced lung eosinophilia, ultimately limiting the metabolic fitness of NK cells. Therapeutic targeting of IL-33 or IL-5 reversed NK cell suppression and alleviated cancer burden. Thus, we reveal an important function of IL-33 and ILC2s in promoting tumor metastasis via their capacity to suppress innate type 1 immunity.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Células Asesinas Naturales / Linfocitos / Eosinófilos / Pulmón / Neoplasias Pulmonares Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Nat Immunol Asunto de la revista: ALERGIA E IMUNOLOGIA Año: 2020 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Células Asesinas Naturales / Linfocitos / Eosinófilos / Pulmón / Neoplasias Pulmonares Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Nat Immunol Asunto de la revista: ALERGIA E IMUNOLOGIA Año: 2020 Tipo del documento: Article Pais de publicación: Estados Unidos