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EBioMedicine. 2015 Aug 13;2(10):1364-76. doi: 10.1016/j.ebiom.2015.08.021. eCollection 2015 Oct.

Identification of Anti-tumor Cells Carrying Natural Killer (NK) Cell Antigens in Patients With Hematological Cancers.

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INSERM U1183, Université de Montpellier, UFR Médecine, Montpellier, France.
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.
Inmunogenética-HLA, Hospital Univ. Puerta de Hierro, Manuel de Falla 1, 28220 Majadahonda, Madrid, Spain.
CNRS UMR 5164, Université Bordeaux, 33076 Bordeaux, France.
Département d'Hématologie Clinique, CHU Montpellier, Université Montpellier, 80 Avenue Augustin Fliche, 34295 Montpellier, France.
INSERM U1183, Université de Montpellier, UFR Médecine, Montpellier, France ; Institut for Regenerative Medicine and Biotherapy (IRMB), CHU Montpellier, Montpellier 34295, France.


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.


CD45; Cytotoxicity; Hematological cancer; NK cell; Trogocytosis

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