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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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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DOI: https://doi.org/10.1007/s00262-015-1720-6