DOI . ORG {
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Title[redir]:
Tumour-derived PGD2 and NKp30-B7H6 engagement drives an immunosuppressive ILC2-MDSC axis | Nature Communications
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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Keywords {🔍}
apl, cells, ilc, ilcs, mice, pubmed, patients, cell, fig, article, pgd, human, google, scholar, cancer, cas, mmdscs, blood, atra, nkp, prostate, expression, innate, lymphoid, frequencies, anticd, analysis, axis, levels, test, central, treatment, lines, immunosuppressive, healthy, data, increased, peripheral, supplementary, model, donors, biolegend, nature, tumour, blasts, antibody, samples, flow, blocking, mouse,
Topics {✒️}
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.
datePublished:2017-09-19T00:00:00Z
dateModified:2017-09-19T00:00:00Z
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license:http://creativecommons.org/licenses/by/4.0/
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Cancer microenvironment
Cytokines
Immune evasion
Innate lymphoid cells
Science
Humanities and Social Sciences
multidisciplinary
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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.
datePublished:2017-09-19T00:00:00Z
dateModified:2017-09-19T00:00:00Z
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Cancer microenvironment
Cytokines
Immune evasion
Innate lymphoid cells
Science
Humanities and Social Sciences
multidisciplinary
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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 âSerà gnoliâ, 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 âSerà gnoliâ, University of Bologna, Bologna, Italy
name:Department of Specialistic, Diagnostic and Experimental Medicine, Institute of Hematology âSerà gnoliâ, 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 âSerà gnoliâ, 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 âSerà gnoliâ, 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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