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CD56 as a marker of an ILC1-like population with NK cell properties that is functionally impaired in AML.

  • Salomé B Department of Oncology UNIL CHUV, University of Lausanne, Lausanne, Switzerland.
  • Gomez-Cadena A Department of Oncology UNIL CHUV, University of Lausanne, Lausanne, Switzerland.
  • Loyon R Department of Oncology UNIL CHUV, University of Lausanne, Lausanne, Switzerland.
  • Suffiotti M Department of Oncology UNIL CHUV, University of Lausanne, Lausanne, Switzerland.
  • Salvestrini V Department of Specialistic, Diagnostic and Experimental Medicine, Institute of Hematology "Seràgnoli," University Bologna, Bologna, Italy.
  • Wyss T Department of Oncology UNIL CHUV, University of Lausanne, Lausanne, Switzerland.
  • Vanoni G Department of Oncology UNIL CHUV, University of Lausanne, Lausanne, Switzerland.
  • Ruan DF Department of Oncological Sciences, Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY.
  • Rossi M Cancer Center IRCCS Humanitas Research Hospital, Milan, Italy.
  • Tozzo A Pediatric Department, University of Insubria, Varese, Italy.
  • Tentorio P Unit of Clinical and Experimental Immunology, Humanitas Clinical and Research Center, Rozzano-Milan, Italy.
  • Bruni E Unit of Clinical and Experimental Immunology, Humanitas Clinical and Research Center, Rozzano-Milan, Italy.
  • Riether C Department of Medical Oncology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
  • Jacobsen EM Department of Pediatrics, University Medical Center Ulm, Ulm, Germany.
  • Jandus P Division of Immunology and Allergology, Department of Medicine, University Hospital and Medical Faculty, Geneva, Switzerland.
  • Conrad C Department of Dermatology, University Hospital CHUV, Lausanne, Switzerland.
  • Hoenig M Department of Pediatrics, University Medical Center Ulm, Ulm, Germany.
  • Schulz A Department of Pediatrics, University Medical Center Ulm, Ulm, Germany.
  • Michaud K University Center of Legal Medicine Lausanne-Geneva, Lausanne University Hospital, University of Lausanne, Lausanne, Switzerland.
  • Della Porta MG Cancer Center IRCCS Humanitas Research Hospital, Milan, Italy.
  • Salvatore S Pediatric Department, University of Insubria, Varese, Italy.
  • Ho PC Department of Oncology UNIL CHUV, University of Lausanne, Lausanne, Switzerland.
  • Gfeller D Department of Oncology UNIL CHUV, University of Lausanne, Lausanne, Switzerland.
  • Ochsenbein A Department of Medical Oncology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
  • Mavilio D Unit of Clinical and Experimental Immunology, Humanitas Clinical and Research Center, Rozzano-Milan, Italy.
  • Curti A Institute of Hematology L. e A. Seràgnoli, Department of Hematology and Oncology, Azienda Ospedaliero-Universitaria S. Orsola-Malpighi, Bologna, Italy.
  • Marcenaro E Department of Experimental Medicine and Centre of Excellence for Biomedical Research, University of Genoa, Genoa, Italy; and.
  • Steinle A Institute for Molecular Medicine, Goethe University Frankfurt, Frankfurt, Germany.
  • Horowitz A Department of Oncological Sciences, Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY.
  • Romero P Department of Oncology UNIL CHUV, University of Lausanne, Lausanne, Switzerland.
  • Trabanelli S Department of Oncology UNIL CHUV, University of Lausanne, Lausanne, Switzerland.
  • Jandus C Department of Oncology UNIL CHUV, University of Lausanne, Lausanne, Switzerland.
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  • 2019-11-26
Published in:
  • Blood advances. - 2019
Biomarkers
CD56 Antigen
Cytotoxicity, Immunologic
Gene Expression Profiling
Humans
Immunity, Innate
Killer Cells, Natural
Leukemia, Myeloid, Acute
Lymphocyte Subsets
Receptors, IgG
Signal Transduction
Transcriptome
English An understanding of natural killer (NK) cell physiology in acute myeloid leukemia (AML) has led to the use of NK cell transfer in patients, demonstrating promising clinical results. However, AML is still characterized by a high relapse rate and poor overall survival. In addition to conventional NKs that can be considered the innate counterparts of CD8 T cells, another family of innate lymphocytes has been recently described with phenotypes and functions mirroring those of helper CD4 T cells. Here, in blood and tissues, we identified a CD56+ innate cell population harboring mixed transcriptional and phenotypic attributes of conventional helper innate lymphoid cells (ILCs) and lytic NK cells. These CD56+ ILC1-like cells possess strong cytotoxic capacities that are impaired in AML patients at diagnosis but are restored upon remission. Their cytotoxicity is KIR independent and relies on the expression of TRAIL, NKp30, NKp80, and NKG2A. However, the presence of leukemic blasts, HLA-E-positive cells, and/or transforming growth factor-β1 (TGF-β1) strongly affect their cytotoxic potential, at least partially by reducing the expression of cytotoxic-related molecules. Notably, CD56+ ILC1-like cells are also present in the NK cell preparations used in NK transfer-based clinical trials. Overall, we identified an NK cell-related CD56+ ILC population involved in tumor immunosurveillance in humans, and we propose that restoring their functions with anti-NKG2A antibodies and/or small molecules inhibiting TGF-β1 might represent a novel strategy for improving current immunotherapies.
Language
  • English
Open access status
gold
Identifiers
Persistent URL
https://sonar.ch/global/documents/5933
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