title: Identification of Anti-tumor Cells Carrying Natural Killer (NK) Cell Antigens in Patients With Hematological Cancers.
abstract: Natural killer (NK) cells, a cytotoxic lymphocyte lineage, are able to kill tumor cells in vitro and in mouse models. However, whether these cells display an anti-tumor activity in cancer patients has not been demonstrated. Here we have addressed this issue in patients with several hematological cancers. We found a population of highly activated CD56(dim)CD16(+) NK cells that have recently degranulated, evidence of killing activity, and it is absent in healthy donors. A high percentage of these cells expressed natural killer cell p46-related protein (NKp46), natural-killer group 2, member D (NKG2D) and killer inhibitory receptors (KIRs) and a low percentage expressed NKG2A and CD94. They are also characterized by a high metabolic activity and active proliferation. Notably, we found that activated NK cells from hematological cancer patients have non-NK tumor cell antigens on their surface, evidence of trogocytosis during tumor cell killing. Finally, we found that these activated NK cells are distinguished by their CD45RA(+)RO(+) phenotype, as opposed to non-activated cells in patients or in healthy donors displaying a CD45RA(+)RO(-) phenotype similar to naïve T cells. In summary, we show that CD45RA(+)RO(+) cells, which resemble a unique NK population, have recognized tumor cells and degranulate in patients with hematological neoplasias.
authors.affiliation: INSERM U1183, Université de Montpellier, UFR Médecine, Montpellier, France.
authors.forename: Ewelina
authors.initials: E
authors.lastname: Krzywinska
authors.affiliation: INSERM U1183, Université de Montpellier, UFR Médecine, Montpellier, France.
authors.forename: Nerea
authors.initials: N
authors.lastname: Allende-Vega
authors.affiliation: INSERM U1183, Université de Montpellier, UFR Médecine, Montpellier, France.
authors.forename: Amelie
authors.initials: A
authors.lastname: Cornillon
authors.affiliation: INSERM U1183, Université de Montpellier, UFR Médecine, Montpellier, France.
authors.forename: Dang-Nghiem
authors.initials: DN
authors.lastname: Vo
authors.affiliation: Laboratory of Rare Human Circulating Cells (LCCRH), Department of Cellular and Tissular Biopathology of Tumors, University Medical Centre, Montpellier, France ; EA2415 - Help for Personalized Decision: Methodological Aspects, University Institute of Clinical Research, Montpellier University, Montpellier, France.
authors.forename: Laure
authors.initials: L
authors.lastname: Cayrefourcq
authors.affiliation: Laboratory of Rare Human Circulating Cells (LCCRH), Department of Cellular and Tissular Biopathology of Tumors, University Medical Centre, Montpellier, France ; EA2415 - Help for Personalized Decision: Methodological Aspects, University Institute of Clinical Research, Montpellier University, Montpellier, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Panabieres
authors.affiliation: Inmunogenética-HLA, Hospital Univ. Puerta de Hierro, Manuel de Falla 1, 28220 Majadahonda, Madrid, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Vilches
authors.affiliation: CNRS UMR 5164, Université Bordeaux, 33076 Bordeaux, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Déchanet-Merville
authors.affiliation: Département d'Hématologie Clinique, CHU Montpellier, Université Montpellier, 80 Avenue Augustin Fliche, 34295 Montpellier, France.
authors.forename: Yosr
authors.initials: Y
authors.lastname: Hicheri
authors.affiliation: Département d'Hématologie Clinique, CHU Montpellier, Université Montpellier, 80 Avenue Augustin Fliche, 34295 Montpellier, France.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Rossi
authors.affiliation: Département d'Hématologie Clinique, CHU Montpellier, Université Montpellier, 80 Avenue Augustin Fliche, 34295 Montpellier, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Cartron
authors.affiliation: INSERM U1183, Université de Montpellier, UFR Médecine, Montpellier, France ; Institut for Regenerative Medicine and Biotherapy (IRMB), CHU Montpellier, Montpellier 34295, France.
authors.forename: Martin
authors.initials: M
authors.lastname: Villalba
mesh_terms: D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism*; D015415:Biomarkers; D016022:Case-Control Studies; D002450:Cell Communication; D015550:Cell Degranulation / Q000276:immunology; D019337:Hematologic Neoplasms / Q000276:immunology* / Q000378:metabolism* / Q000821:virology; D006801:Humans; D016130:Immunophenotyping; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism*; D017493:Leukocyte Common Antigens / Q000378:metabolism; D051379:Mice; D010641:Phenotype; D020033:Protein Isoforms
chemical_list: D000954:Antigens, Surface; D015415:Biomarkers; D020033:Protein Isoforms; D017493:Leukocyte Common Antigens
keywords: CD45; Cytotoxicity; Hematological cancer; NK cell; Trogocytosis