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Natural killer cell immunosenescence in acute myeloid leukaemia patients: new targets for immunotherapeutic strategies?

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Abstract

Several age-associated changes in natural killer (NK) cell phenotype have been reported that contribute to the defective NK cell response observed in elderly patients. A remodelling of the NK cell compartment occurs in the elderly with a reduction in the output of immature CD56bright cells and an accumulation of highly differentiated CD56dim NK cells. Acute myeloid leukaemia (AML) is generally a disease of older adults. NK cells in AML patients show diminished expression of several activating receptors that contribute to impaired NK cell function and, in consequence, to AML blast escape from NK cell immunosurveillance. In AML patients, phenotypic changes in NK cells have been correlated with disease progression and survival. NK cell-based immunotherapy has emerged as a possibility for the treatment of AML patients. The understanding of age-associated alterations in NK cells is therefore necessary to define adequate therapeutic strategies in older AML patients.

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Abbreviations

AML:

Acute myeloid leukaemia

AML-NK:

Acute myeloid leukaemia patient NK cells

BiKEs:

Bispecific killer engagers

CAR:

Chimeric antigen receptor

CMV:

Cytomegalovirus

DNAM-1:

DNAX accessory molecule-1

HLA:

Human leucocyte antigen

IL:

Interleukin

ILCs:

Innate lymphoid cells

IFN:

Interferon

KIRs:

Killer cell immunoglobulin-like receptors

LAK:

Lymphokine-activated killer

LILRs:

Leucocyte immunoglobulin-like receptors

MHC:

Major histocompatibility complex

MICA:

MHC class I-related protein A

MICB:

MHC class I-related protein B

NCRs:

Natural cytotoxicity receptors

NEACT:

Non-engrafting alloreactive cellular therapy

NK:

Natural killer

NKG2D:

NK group 2, member D

PBMCs:

Peripheral blood mononuclear cells

TNF:

Tumour necrosis factor

TriKEs:

Trispecific killer engagers

ULBP:

UL-16 binding protein

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Acknowledgments

We apologize to our colleagues whose work was not cited due to space limitations. This work was supported by grants SAF2009-09711 and SAF2013-46161-R (to Raquel Tarazona) from the Ministry of Economy and Competitiveness of Spain, PS09/00723 and PI13/02691 (to Rafael Solana) from Spanish Ministry of Health, CTS-208 from Junta de Andalucia (to Rafael Solana) and grants to INPATT research group (GRU10104) from Junta de Extremadura and University of Extremadura (to Raquel Tarazona and Esther Duran) cofinanced by European Regional Development Funds (FEDER).

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The authors declare that they have no conflict of interest.

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    Authors and Affiliations

    1. Immunology Unit, University of Extremadura, Cáceres, Spain

      Beatriz Sanchez-Correa, Javier G. Casado, Sara Morgado & Raquel Tarazona

    2. Department of Immunology, IMIBIC, Reina Sofia University Hospital, University of Cordoba, Avenida Menendez Pidal s/n, 14004, Córdoba, Spain

      Carmen Campos, Alejandra Pera & Rafael Solana

    3. Department of Hematology, Hospital San Pedro de Alcantara, Cáceres, Spain

      Juan M. Bergua, Maria Jose Arcos & Helena Bañas

    4. Stem Cell Therapy Unit, Minimally Invasive Surgery Centre Jesus Uson, Cáceres, Spain

      Javier G. Casado

    5. Histology and Pathology Unit, Faculty of Veterinary, University of Extremadura, Cáceres, Spain

      Esther Duran

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    1. Beatriz Sanchez-Correa
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    Correspondence to Rafael Solana.

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    Rafael Solana and Raquel Tarazona are senior authors and have contributed equally to the manuscript.

    This article is part of the Symposium-in-Writing “Natural killer cells, ageing and cancer”, a series of papers published in Cancer Immunology, Immunotherapy.

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    Sanchez-Correa, B., Campos, C., Pera, A. et al. Natural killer cell immunosenescence in acute myeloid leukaemia patients: new targets for immunotherapeutic strategies?. Cancer Immunol Immunother 65, 453–463 (2016). https://doi.org/10.1007/s00262-015-1720-6

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