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         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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         Cancer microenvironment
         Cytokines
         Immune evasion
         Innate lymphoid cells
         Science
         Humanities and Social Sciences
         multidisciplinary
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            address:
               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:Lausanne University Hospital (CHUV)
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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:Bérengère Salomé
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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
            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 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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      name:Cristina Papayannidis
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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:Christine Kühne-Center for Allergy Research and Education
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               name:Christine Kühne-Center for Allergy Research and Education, Davos, Switzerland
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      name:Irene Pizzitola
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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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      name:Perrine Bohner
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            address:
               name:Urology Research Unit, Lausanne University Hospital (CHUV), Lausanne, Switzerland
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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:Rani Pallavi
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            name:European Institute of Oncology
            address:
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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
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            name:Humanitas University
            address:
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            name:Ospedale Papa Giovanni XXIII
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               name:Hematology and Bone Marrow Transplant Unit, Ospedale Papa Giovanni XXIII, Bergamo, Italy
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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
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            address:
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            address:
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               name:Divisione di Ricerca di Medicina Rigenerativa, Terapia Cellulare e Genica IRCCS, San Raffaele Hospital, Milano, Italy
               type:PostalAddress
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      name:David Gfeller
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            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
               type:PostalAddress
            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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            type:Organization
      name:Luca Mazzarella
      affiliation:
            name:European Institute of Oncology
            address:
               name:Department of Experimental Oncology, European Institute of Oncology, Milan, Italy
               type:PostalAddress
            type:Organization
            name:European Institute of Oncology
            address:
               name:Division of Innovative Therapies, European Institute of Oncology, Milan, Italy
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            type:Organization
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            name:European Institute of Oncology
            address:
               name:Department of Experimental Oncology, European Institute of Oncology, Milan, Italy
               type:PostalAddress
            type:Organization
      name:Pier Giuseppe Pelicci
      affiliation:
            name:European Institute of Oncology
            address:
               name:Department of Experimental Oncology, European Institute of Oncology, Milan, Italy
               type:PostalAddress
            type:Organization
      name:Emanuela Marcenaro
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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
      name:Andrew N. J. McKenzie
      affiliation:
            name:MRC Laboratory of Molecular Biology
            address:
               name:MRC Laboratory of Molecular Biology, Cambridge, UK
               type:PostalAddress
            type:Organization
      name:Dominique Vanhecke
      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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