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nature portfolio privacy policy pe-cy7-conjugated anti-hla-dr pacific blue-conjugated anti-cd44 pgd2-ilc2-il-13-m-mdsc immunosuppressive axis advertising apc-efluor780-conjugated anti-ly6c pe-cy7-conjugated anti-cd49d pml-rara fusion protein alexafluor700-conjugated anti-il-17a male tramp-fvb/nj mice30 apc-efluor780-conjugated anti-cd56 apc-efluor780-conjugated anti-gr1 nature pe-texasred-conjugated anti-cd56 pe-conjugated anti-human tcrαβ valuable tools apc-cy7-conjugated anti-cd5 pacific blue-conjugated anti-cd14 ilc2-il-13-m-mdsc immunosuppressive axis inhibit graft-versus-host disease pe-cy7-conjugated anti-cd45 pe-af610-conjugated anti-cd19 pe-af610-conjugated anti-cd3 social media percp-efluor710-conjugated anti-ckit myeloid-derived suppressor cells pe-conjugated anti-il-13rα1 medical-biological research 15c165 pe-cy7-conjugated ifn-γ ilc2-il-13-m-mdsc network reprints exert pro-tumoural activity ilc2 supernatant-induced m-mdscs ilc2-m-mdsc immunosuppressive axis pe-cy7-conjugated cd1a il-13rα1 expressing cells quantitative real-time pcr pe-conjugated anti-6b11 pe-conjugated anti-st2 lin−cd127+crth2−ckit+nkp46+ lin−cd127+crth2−ckit+nkp46− acute promyelocytic leukemia fitc-conjugated anti-cd3e alexa647-conjugated anti-cd62l alexafluor647-conjugated anti-ki-67 bona fide m-mdscs anti-il-13 neutralizing antibody 65 mg/kg body weight 5 mg/kg body weight

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         headline:Tumour-derived PGD2 and NKp30-B7H6 engagement drives an immunosuppressive ILC2-MDSC axis
         description:Group 2 innate lymphoid cells (ILC2s) are involved in human diseases, such as allergy, atopic dermatitis and nasal polyposis, but their function in human cancer remains unclear. Here we show that, in acute promyelocytic leukaemia (APL), ILC2s are increased and hyper-activated through the interaction of CRTH2 and NKp30 with elevated tumour-derived PGD2 and B7H6, respectively. ILC2s, in turn, activate monocytic myeloid-derived suppressor cells (M-MDSCs) via IL-13 secretion. Upon treating APL with all-trans retinoic acid and achieving complete remission, the levels of PGD2, NKp30, ILC2s, IL-13 and M-MDSCs are restored. Similarly, disruption of this tumour immunosuppressive axis by specifically blocking PGD2, IL-13 and NKp30 partially restores ILC2 and M-MDSC levels and results in increased survival. Thus, using APL as a model, we uncover a tolerogenic pathway that may represent a relevant immunosuppressive, therapeutic targetable, mechanism operating in various human tumour types, as supported by our observations in prostate cancer. Group 2 innate lymphoid cells (ILC2s) modulate inflammatory and allergic responses, but their function in cancer immunity is still unclear. Here the authors show that, in acute promyelocytic leukaemia, tumour-activated ILC2s secrete IL-13 to induce myeloid-derived suppressor cells and support tumour growth.
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      headline:Tumour-derived PGD2 and NKp30-B7H6 engagement drives an immunosuppressive ILC2-MDSC axis
      description:Group 2 innate lymphoid cells (ILC2s) are involved in human diseases, such as allergy, atopic dermatitis and nasal polyposis, but their function in human cancer remains unclear. Here we show that, in acute promyelocytic leukaemia (APL), ILC2s are increased and hyper-activated through the interaction of CRTH2 and NKp30 with elevated tumour-derived PGD2 and B7H6, respectively. ILC2s, in turn, activate monocytic myeloid-derived suppressor cells (M-MDSCs) via IL-13 secretion. Upon treating APL with all-trans retinoic acid and achieving complete remission, the levels of PGD2, NKp30, ILC2s, IL-13 and M-MDSCs are restored. Similarly, disruption of this tumour immunosuppressive axis by specifically blocking PGD2, IL-13 and NKp30 partially restores ILC2 and M-MDSC levels and results in increased survival. Thus, using APL as a model, we uncover a tolerogenic pathway that may represent a relevant immunosuppressive, therapeutic targetable, mechanism operating in various human tumour types, as supported by our observations in prostate cancer. Group 2 innate lymphoid cells (ILC2s) modulate inflammatory and allergic responses, but their function in cancer immunity is still unclear. Here the authors show that, in acute promyelocytic leukaemia, tumour-activated ILC2s secrete IL-13 to induce myeloid-derived suppressor cells and support tumour growth.
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         Cytokines
         Immune evasion
         Innate lymphoid cells
         Science
         Humanities and Social Sciences
         multidisciplinary
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               name:Ludwig Institute for Cancer Research, Department of Fundamental Oncology, University of Lausanne, Epalinges, Switzerland
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      name:Mathieu F. Chevalier
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      name:Amaia Martinez-Usatorre
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            name:University of Lausanne
            address:
               name:Ludwig Institute for Cancer Research, Department of Fundamental Oncology, University of Lausanne, Epalinges, Switzerland
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            type:Organization
      name:Alejandra Gomez-Cadena
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            name:University of Lausanne
            address:
               name:Ludwig Institute for Cancer Research, Department of Fundamental Oncology, University of Lausanne, Epalinges, Switzerland
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            name:University of Lausanne
            address:
               name:Ludwig Institute for Cancer Research, Department of Fundamental Oncology, University of Lausanne, Epalinges, Switzerland
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            type:Organization
      name:Mariangela Lecciso
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            name:University of Bologna
            address:
               name:Department of Specialistic, Diagnostic and Experimental Medicine, Institute of Hematology “Seràgnoli”, University of Bologna, Bologna, Italy
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            name:University of Bologna
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               name:Department of Specialistic, Diagnostic and Experimental Medicine, Institute of Hematology “Seràgnoli”, University of Bologna, Bologna, Italy
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            name:University of Lausanne
            address:
               name:Ludwig Institute for Cancer Research, Department of Fundamental Oncology, University of Lausanne, Epalinges, Switzerland
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            name:University of Lausanne
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               name:Ludwig Institute for Cancer Research, Department of Fundamental Oncology, University of Lausanne, Epalinges, Switzerland
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            name:University of Bologna
            address:
               name:Department of Specialistic, Diagnostic and Experimental Medicine, Institute of Hematology “Seràgnoli”, University of Bologna, Bologna, Italy
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            type:Organization
      name:Hideaki Morita
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            name:University of Zurich
            address:
               name:Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
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            name:University of Lausanne
            address:
               name:Ludwig Institute for Cancer Research, Department of Fundamental Oncology, University of Lausanne, Epalinges, Switzerland
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            address:
               name:Ludwig Institute for Cancer Research, Department of Fundamental Oncology, University of Lausanne, Epalinges, Switzerland
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            address:
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      name:Elena Bruni
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            name:University of Milan
            address:
               name:Department of Medical Biotechnologies and Translational Medicine, University of Milan, Milan, Italy
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            name:Humanitas Clinical and Research Center
            address:
               name:Unit of Clinical and Experimental Immunology, Humanitas Clinical and Research Center, Rozzano-Milan, Italy
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      name:Mukul Girotra
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            name:University of Lausanne
            address:
               name:Ludwig Institute for Cancer Research, Department of Fundamental Oncology, University of Lausanne, Epalinges, Switzerland
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            name:European Institute of Oncology
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      name:Gabriela M. Baerlocher
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            name:Bern University Hospital, University of Bern
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            name:Humanitas Clinical and Research Center
            address:
               name:Humanitas Cancer Center, Humanitas Clinical and Research Center, Rozzano-Milan, Italy
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            name:Humanitas University
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            address:
               name:Humanitas Cancer Center, Humanitas Clinical and Research Center, Rozzano-Milan, Italy
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            name:Humanitas University
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               name:Department of Biomedical Sciences, Humanitas University, Rozzano-Milan, Italy
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            address:
               name:Humanitas Cancer Center, Humanitas Clinical and Research Center, Rozzano-Milan, Italy
               type:PostalAddress
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            name:Humanitas University
            address:
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      name:Orietta Spinelli
      affiliation:
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               name:Hematology and Bone Marrow Transplant Unit, Ospedale Papa Giovanni XXIII, Bergamo, Italy
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               name:Università Statale di Milano, Milan, Italy
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            address:
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            address:
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               type:PostalAddress
            type:Organization
      name:David Gfeller
      affiliation:
            name:University of Lausanne
            address:
               name:Ludwig Institute for Cancer Research, Department of Fundamental Oncology, University of Lausanne, Epalinges, Switzerland
               type:PostalAddress
            type:Organization
            name:Swiss Institute of Bioinformatics (SIB)
            address:
               name:Swiss Institute of Bioinformatics (SIB), Lausanne, Switzerland
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            type:Organization
      name:Cezmi A. Akdis
      affiliation:
            name:University of Zurich
            address:
               name:Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
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            address:
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            address:
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            name:European Institute of Oncology
            address:
               name:Department of Experimental Oncology, European Institute of Oncology, Milan, Italy
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            type:Organization
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      affiliation:
            name:University of Genoa
            address:
               name:Department of Experimental Medicine (DI.ME.S.)-Section of Histology, and Center of Excellent of Biomedical Research (CEBR), University of Genoa, Genoa, Italy
               type:PostalAddress
            type:Organization
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      affiliation:
            name:MRC Laboratory of Molecular Biology
            address:
               name:MRC Laboratory of Molecular Biology, Cambridge, UK
               type:PostalAddress
            type:Organization
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      affiliation:
            name:University of Lausanne
            address:
               name:Ludwig Institute for Cancer Research, Department of Fundamental Oncology, University of Lausanne, Epalinges, Switzerland
               type:PostalAddress
            type:Organization
      name:George Coukos
      affiliation:
            name:University of Lausanne
            address:
               name:Ludwig Institute for Cancer Research, Department of Fundamental Oncology, University of Lausanne, Epalinges, Switzerland
               type:PostalAddress
            type:Organization
      name:Domenico Mavilio
      url:http://orcid.org/0000-0001-6147-0952
      affiliation:
            name:University of Milan
            address:
               name:Department of Medical Biotechnologies and Translational Medicine, University of Milan, Milan, Italy
               type:PostalAddress
            type:Organization
            name:Humanitas Clinical and Research Center
            address:
               name:Unit of Clinical and Experimental Immunology, Humanitas Clinical and Research Center, Rozzano-Milan, Italy
               type:PostalAddress
            type:Organization
      name:Antonio Curti
      affiliation:
            name:University of Bologna
            address:
               name:Department of Specialistic, Diagnostic and Experimental Medicine, Institute of Hematology “Seràgnoli”, University of Bologna, Bologna, Italy
               type:PostalAddress
            type:Organization
      name:Laurent Derré
      url:http://orcid.org/0000-0002-3403-161X
      affiliation:
            name:Lausanne University Hospital (CHUV)
            address:
               name:Urology Research Unit, Lausanne University Hospital (CHUV), Lausanne, Switzerland
               type:PostalAddress
            type:Organization
      name:Camilla Jandus
      url:http://orcid.org/0000-0002-7405-5747
      affiliation:
            name:University of Lausanne
            address:
               name:Ludwig Institute for Cancer Research, Department of Fundamental Oncology, University of Lausanne, Epalinges, Switzerland
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:Ludwig Institute for Cancer Research, Department of Fundamental Oncology, University of Lausanne, Epalinges, Switzerland
      name:Urology Research Unit, Lausanne University Hospital (CHUV), Lausanne, Switzerland
      name:Ludwig Institute for Cancer Research, Department of Fundamental Oncology, University of Lausanne, Epalinges, Switzerland
      name:Ludwig Institute for Cancer Research, Department of Fundamental Oncology, University of Lausanne, Epalinges, Switzerland
      name:Ludwig Institute for Cancer Research, Department of Fundamental Oncology, University of Lausanne, Epalinges, Switzerland
      name:Department of Specialistic, Diagnostic and Experimental Medicine, Institute of Hematology “Seràgnoli”, University of Bologna, Bologna, Italy
      name:Department of Specialistic, Diagnostic and Experimental Medicine, Institute of Hematology “Seràgnoli”, University of Bologna, Bologna, Italy
      name:Ludwig Institute for Cancer Research, Department of Fundamental Oncology, University of Lausanne, Epalinges, Switzerland
      name:Ludwig Institute for Cancer Research, Department of Fundamental Oncology, University of Lausanne, Epalinges, Switzerland
      name:Swiss Institute of Bioinformatics (SIB), Lausanne, Switzerland
      name:Department of Specialistic, Diagnostic and Experimental Medicine, Institute of Hematology “Seràgnoli”, University of Bologna, Bologna, Italy
      name:Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
      name:Christine Kühne-Center for Allergy Research and Education, Davos, Switzerland
      name:Ludwig Institute for Cancer Research, Department of Fundamental Oncology, University of Lausanne, Epalinges, Switzerland
      name:Ludwig Institute for Cancer Research, Department of Fundamental Oncology, University of Lausanne, Epalinges, Switzerland
      name:Urology Research Unit, Lausanne University Hospital (CHUV), Lausanne, Switzerland
      name:Department of Medical Biotechnologies and Translational Medicine, University of Milan, Milan, Italy
      name:Unit of Clinical and Experimental Immunology, Humanitas Clinical and Research Center, Rozzano-Milan, Italy
      name:Ludwig Institute for Cancer Research, Department of Fundamental Oncology, University of Lausanne, Epalinges, Switzerland
      name:Department of Experimental Oncology, European Institute of Oncology, Milan, Italy
      name:Department of Experimental Oncology, European Institute of Oncology, Milan, Italy
      name:Department of Hematology, Bern University Hospital, University of Bern, Bern, Switzerland
      name:Department of Hematology, Bern University Hospital, University of Bern, Bern, Switzerland
      name:Humanitas Cancer Center, Humanitas Clinical and Research Center, Rozzano-Milan, Italy
      name:Department of Biomedical Sciences, Humanitas University, Rozzano-Milan, Italy
      name:Humanitas Cancer Center, Humanitas Clinical and Research Center, Rozzano-Milan, Italy
      name:Department of Biomedical Sciences, Humanitas University, Rozzano-Milan, Italy
      name:Humanitas Cancer Center, Humanitas Clinical and Research Center, Rozzano-Milan, Italy
      name:Department of Biomedical Sciences, Humanitas University, Rozzano-Milan, Italy
      name:Hematology and Bone Marrow Transplant Unit, Ospedale Papa Giovanni XXIII, Bergamo, Italy
      name:Hematology and Bone Marrow Transplant Unit, Ospedale Papa Giovanni XXIII, Bergamo, Italy
      name:Università Statale di Milano, Milan, Italy
      name:Dipartimento per la Salute della Donna e del Bambino, Clinica di Oncoematologia Pediatrica, University of Padova, Padova, Italy
      name:Dipartimento per la Salute della Donna e del Bambino, Clinica di Oncoematologia Pediatrica, University of Padova, Padova, Italy
      name:Immunoematologia e Medicina Trasfusionale, Laboratorio Ematologia Molecolare, Biobanca Neoplasie Ematologiche, San Raffaele Hospital, Milano, Italy
      name:Divisione di Ricerca di Medicina Rigenerativa, Terapia Cellulare e Genica IRCCS, San Raffaele Hospital, Milano, Italy
      name:Ludwig Institute for Cancer Research, Department of Fundamental Oncology, University of Lausanne, Epalinges, Switzerland
      name:Swiss Institute of Bioinformatics (SIB), Lausanne, Switzerland
      name:Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland
      name:Department of Experimental Oncology, European Institute of Oncology, Milan, Italy
      name:Division of Innovative Therapies, European Institute of Oncology, Milan, Italy
      name:Department of Experimental Oncology, European Institute of Oncology, Milan, Italy
      name:Department of Experimental Oncology, European Institute of Oncology, Milan, Italy
      name:Department of Experimental Medicine (DI.ME.S.)-Section of Histology, and Center of Excellent of Biomedical Research (CEBR), University of Genoa, Genoa, Italy
      name:MRC Laboratory of Molecular Biology, Cambridge, UK
      name:Ludwig Institute for Cancer Research, Department of Fundamental Oncology, University of Lausanne, Epalinges, Switzerland
      name:Ludwig Institute for Cancer Research, Department of Fundamental Oncology, University of Lausanne, Epalinges, Switzerland
      name:Department of Medical Biotechnologies and Translational Medicine, University of Milan, Milan, Italy
      name:Unit of Clinical and Experimental Immunology, Humanitas Clinical and Research Center, Rozzano-Milan, Italy
      name:Department of Specialistic, Diagnostic and Experimental Medicine, Institute of Hematology “Seràgnoli”, University of Bologna, Bologna, Italy
      name:Urology Research Unit, Lausanne University Hospital (CHUV), Lausanne, Switzerland
      name:Ludwig Institute for Cancer Research, Department of Fundamental Oncology, University of Lausanne, Epalinges, Switzerland

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