Blood Advances (Nov 2019)
CD56 as a marker of an ILC1-like population with NK cell properties that is functionally impaired in AML
- Bérengère Salomé,
- Alejandra Gomez-Cadena,
- Romain Loyon,
- Madeleine Suffiotti,
- Valentina Salvestrini,
- Tania Wyss,
- Giulia Vanoni,
- Dan Fu Ruan,
- Marianna Rossi,
- Alessandra Tozzo,
- Paolo Tentorio,
- Elena Bruni,
- Carsten Riether,
- Eva-Maria Jacobsen,
- Peter Jandus,
- Curdin Conrad,
- Manfred Hoenig,
- Ansgar Schulz,
- Katarzyna Michaud,
- Matteo Giovanni Della Porta,
- Silvia Salvatore,
- Ping-Chih Ho,
- David Gfeller,
- Adrian Ochsenbein,
- Domenico Mavilio,
- Antonio Curti,
- Emanuela Marcenaro,
- Alexander Steinle,
- Amir Horowitz,
- Pedro Romero,
- Sara Trabanelli,
- Camilla Jandus
Affiliations
- Bérengère Salomé
- Department of Oncology UNIL CHUV, University of Lausanne, Lausanne, Switzerland;; Department of Oncological Sciences, Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY;
- Alejandra Gomez-Cadena
- Department of Oncology UNIL CHUV, University of Lausanne, Lausanne, Switzerland;; Ludwig Institute for Cancer Research, University of Lausanne, Lausanne, Switzerland;
- Romain Loyon
- Department of Oncology UNIL CHUV, University of Lausanne, Lausanne, Switzerland;
- Madeleine Suffiotti
- Department of Oncology UNIL CHUV, University of Lausanne, Lausanne, Switzerland;; Ludwig Institute for Cancer Research, University of Lausanne, Lausanne, Switzerland;; Swiss Institute of Bioinformatics, Lausanne, Switzerland;
- Valentina Salvestrini
- Department of Specialistic, Diagnostic and Experimental Medicine, Institute of Hematology “Seràgnoli,” University Bologna, Bologna, Italy;
- Tania Wyss
- Department of Oncology UNIL CHUV, University of Lausanne, Lausanne, Switzerland;; Ludwig Institute for Cancer Research, University of Lausanne, Lausanne, Switzerland;; Swiss Institute of Bioinformatics, Lausanne, Switzerland;
- Giulia Vanoni
- Department of Oncology UNIL CHUV, University of Lausanne, Lausanne, Switzerland;; Ludwig Institute for Cancer Research, University of Lausanne, Lausanne, Switzerland;
- Dan Fu Ruan
- Department of Oncological Sciences, Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY;
- Marianna Rossi
- Cancer Center IRCCS Humanitas Research Hospital, Milan, Italy;
- Alessandra Tozzo
- Pediatric Department, University of Insubria, Varese, Italy;
- Paolo Tentorio
- Unit of Clinical and Experimental Immunology, Humanitas Clinical and Research Center, Rozzano-Milan, Italy;
- Elena Bruni
- Unit of Clinical and Experimental Immunology, Humanitas Clinical and Research Center, Rozzano-Milan, Italy;; Department of Medical Biotechnologies and Translational Medicine, University of Milan, Milan, Italy;
- Carsten Riether
- Department of Medical Oncology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland;
- Eva-Maria Jacobsen
- Department of Pediatrics, University Medical Center Ulm, Ulm, Germany;
- Peter Jandus
- Division of Immunology and Allergology, Department of Medicine, University Hospital and Medical Faculty, Geneva, Switzerland;
- Curdin Conrad
- Department of Dermatology, University Hospital CHUV, Lausanne, Switzerland;; Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland
- Manfred Hoenig
- Department of Pediatrics, University Medical Center Ulm, Ulm, Germany;
- Ansgar Schulz
- Department of Pediatrics, University Medical Center Ulm, Ulm, Germany;
- Katarzyna Michaud
- University Center of Legal Medicine Lausanne-Geneva, Lausanne University Hospital, University of Lausanne, Lausanne, Switzerland;
- Matteo Giovanni Della Porta
- Cancer Center IRCCS Humanitas Research Hospital, Milan, Italy;; Department of Biomedical Sciences, Humanitas University, Milan, Italy;
- Silvia Salvatore
- Pediatric Department, University of Insubria, Varese, Italy;
- Ping-Chih Ho
- Department of Oncology UNIL CHUV, University of Lausanne, Lausanne, Switzerland;; Ludwig Institute for Cancer Research, University of Lausanne, Lausanne, Switzerland;
- David Gfeller
- Department of Oncology UNIL CHUV, University of Lausanne, Lausanne, Switzerland;; Ludwig Institute for Cancer Research, University of Lausanne, Lausanne, Switzerland;; Swiss Institute of Bioinformatics, Lausanne, Switzerland;
- Adrian Ochsenbein
- Department of Medical Oncology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland;
- Domenico Mavilio
- Unit of Clinical and Experimental Immunology, Humanitas Clinical and Research Center, Rozzano-Milan, Italy;; Department of Medical Biotechnologies and Translational Medicine, University of Milan, Milan, Italy;
- Antonio Curti
- Institute of Hematology L. e A. Seràgnoli, Department of Hematology and Oncology, Azienda Ospedaliero-Universitaria S. Orsola-Malpighi, Bologna, Italy;
- Emanuela Marcenaro
- Department of Experimental Medicine and Centre of Excellence for Biomedical Research, University of Genoa, Genoa, Italy
- Alexander Steinle
- Institute for Molecular Medicine, Goethe University Frankfurt, Frankfurt, Germany
- Amir Horowitz
- Department of Oncological Sciences, Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY;
- Pedro Romero
- Department of Oncology UNIL CHUV, University of Lausanne, Lausanne, Switzerland;
- Sara Trabanelli
- Department of Oncology UNIL CHUV, University of Lausanne, Lausanne, Switzerland;; Ludwig Institute for Cancer Research, University of Lausanne, Lausanne, Switzerland;; Sara Trabanelli, University of Lausanne, Chemin des Boveresses 155, 1066 Epalinges, Switzerland;
- Camilla Jandus
- Department of Oncology UNIL CHUV, University of Lausanne, Lausanne, Switzerland;; Ludwig Institute for Cancer Research, University of Lausanne, Lausanne, Switzerland;; Camilla Jandus, University of Lausanne, Chemin des Boveresses 155, 1066 Epalinges, Switzerland
- Journal volume & issue
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Vol. 3,
no. 22
pp. 3674 – 3687
Abstract
Abstract: 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.
