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Age-Associated Alterations on Natural Killer Cells in Acute Myeloid Leukemia Patients

  • Living reference work entry
  • First Online:
Handbook of Immunosenescence

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Abstract

Natural killer (NK) cells were originally defined as lymphocytes characterized by their natural capacity to kill tumor cells and virus-infected cells without the requirement of prior sensitization. NK cells produce cytotoxic molecules such as perforin and granzymes and secrete several cytokines and chemokines that regulate immune function. Aging is associated with alterations in the immune system, a process termed immunosenescence that affects both innate and adaptive immunity. Immunosenescence affects tumor immunosurveillance and consequently may be partly responsible of the age-related increase in cancer incidence. Age is associated with changes in the frequency, phenotype, and distribution of human NK cell subsets. Acute myeloid leukemia (AML) is a hematologic disease that generally affects 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, NK cell phenotype resembles that found in healthy elderly individuals supporting that NK cells from young AML patients are immunosenescent cells probably as consequence of chronic stimulation with activating ligands on leukemic blasts. Therefore, 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. Further understanding of age-associated defects of NK cell function is necessary to define adequate therapeutic strategies in older AML patients.

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Abbreviations

ADCC:

Antibody-dependent cell cytotoxicity

AML:

Acute myeloid leukemia

CAR:

Chimeric antigen receptor

DNAM-1:

DNAX accessory molecule-1

HLA:

Human leukocyte antigen

HMGB-1:

High mobility group protein B1

HSCT:

Allogeneic hematopoietic stem cell transplantation

IFN:

Interferon

IL:

Interleukin

ILC:

Innate lymphoid cells

KIR:

Killer cell immunoglobulin-like receptors

LAG-3:

Lymphocyte activation gene 3 protein

MHC:

Major histocompatibility complex

MLL5:

Mixed-lineage leukemia-5

NCRs:

Natural cytotoxicity receptors

NEACT:

Non-engrafting alloreactive cellular therapy

NK:

Natural killer

PD-1:

Programmed death protein 1

TIGIT:

T-cell immunoreceptor with Ig and ITIM domains

TIM3:

T-cell immunoglobulin domain and mucin domain 3

TNF-α:

Tumor necrosis factor-α

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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 RT) from the Ministry of Economy and Competitiveness of Spain, PS09/00723, PI13/02691 and PI16/01615 (to RS) from Spanish Ministry of Health, and CTS-208 from Junta de Andalucia (to RS) and grants to INPATT research group (GR10104 and GR15183) and IB16164 from Junta de Extremadura and University of Extremadura (to RT) cofinanced by European Regional Development Funds (FEDER).

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Authors and Affiliations

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

    Beatriz Sánchez-Correa & Raquel Tarazona

  2. Maimonides Biomedicine Institute of Cordoba (IMIBIC), Reina Sofia Hospital-University of Cordoba, Cordoba, Spain

    Carmen Campos, Alejandra Pera & Rafael Solana

  3. Brighton and Sussex Medical School, University of Sussex, Brighton, UK

    Alejandra Pera

  4. Hematology Unit, Hospital San Pedro de Alcantara, Caceres, Spain

    Juan M. Bergua

  5. Histology and Pathology Unit, University of Extremadura, Caceres, Spain

    Esther Duran

Authors
  1. Beatriz Sánchez-Correa
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  2. Carmen Campos
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  3. Alejandra Pera
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  4. Juan M. Bergua
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  5. Esther Duran
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  6. Rafael Solana
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  7. Raquel Tarazona
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Corresponding authors

Correspondence to Rafael Solana or Raquel Tarazona .

Editor information

Editors and Affiliations

  1. Division of Geriatrics Research Center on Aging, University of Sherbrooke Dept. of Medicine, Sherbrooke, Québec, Canada

    Tamas Fulop

  2. Dept of Experimental Pathology, University of Bologna, Bologna, Italy

    Claudio Franceschi

  3. Institute for Health and Life Sciences, Tokyo, Japan

    Katsuiku Hirokawa

  4. Center for Medical Research, University of Tübingen, Tübingen, Germany

    Graham Pawelec

Section Editor information

  1. Research Center on Aging, Department of Medicine, Immunology Graduate Programme, Faculty of Medicine, University of Sherbrooke, Sherbrooke, Quebec, Canada

    Tamas Fulop

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Sánchez-Correa, B. et al. (2018). Age-Associated Alterations on Natural Killer Cells in Acute Myeloid Leukemia Patients. In: Fulop, T., Franceschi, C., Hirokawa, K., Pawelec, G. (eds) Handbook of Immunosenescence. Springer, Cham. https://doi.org/10.1007/978-3-319-64597-1_140-1

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  • DOI: https://doi.org/10.1007/978-3-319-64597-1_140-1

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  • Print ISBN: 978-3-319-64597-1

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