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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.

Author information

1
INSERM U1183, Université de Montpellier, UFR Médecine, Montpellier, France.
2
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.
3
Inmunogenética-HLA, Hospital Univ. Puerta de Hierro, Manuel de Falla 1, 28220 Majadahonda, Madrid, Spain.
4
CNRS UMR 5164, Université Bordeaux, 33076 Bordeaux, France.
5
Département d'Hématologie Clinique, CHU Montpellier, Université Montpellier, 80 Avenue Augustin Fliche, 34295 Montpellier, France.
6
INSERM U1183, Université de Montpellier, UFR Médecine, Montpellier, France ; Institut for Regenerative Medicine and Biotherapy (IRMB), CHU Montpellier, Montpellier 34295, France.

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.

KEYWORDS:

CD45; Cytotoxicity; Hematological cancer; NK cell; Trogocytosis

PMID:
26629531
PMCID:
PMC4634619
DOI:
10.1016/j.ebiom.2015.08.021
[Indexed for MEDLINE]
Free PMC Article

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