Natural Killer Cell Immunosenescence and Cancer in the Elderly
Ageing is associated with changes in the immune system that may affect both innate and adaptive immune responses. Well-preserved natural killer (NK) cell cytotoxicity has been considered as a biomarker of healthy ageing and longevity, whereas low NK cytotoxicity is a predictor of morbidity and mortality due to infections. Remodeling of the NK cell compartment occurs in the elderly, probably reflecting the reduction in the output of the immature CD56bright cells and an accumulation of highly differentiated CD56dim CD57+ NK cells. NK cells in the elderly show phenotypic and functional changes as diminished expression of several activating NK cell receptors or decreased proliferative response to cytokines. Age-associated immune deterioration has been recently considered an additional cause for the high incidence of cancer in the elderly since the immune response against tumors goes down with age. Thus, age-associated alterations in NK cell function may constitute a new biomarker associated to the increased incidence of cancer in the elderly.
KeywordsNatural Killer Natural Killer Cell Acute Myeloid Leukemia Major Histocompatibility Complex Class Natural Killer Cell Cytotoxicity
We apologize to our colleagues whose work was not cited due to space limitations. This work was supported by grants PS09/00723 (to R.S.) from Spanish Ministry of Health and SAF2009-09711 from the Ministry of Science and Innovation of Spain and PRI09A029 (to RT) and grants to INPATT research group from Junta de Extremadura (GRU10104) and from University of Extremadura, cofinanced by European Regional Development Fund (FEDER).
- Appay V, Sauce D, Prelog M (2010) The role of the thymus in immunosenescence: lessons from the study of thymectomized individuals. Aging (Albany NY) 2:78–81Google Scholar
- Camous X, Pera A, Solana R et al (2012) NK cells in healthy aging and age-associated diseases. J Biomed Biotechnol 195956Google Scholar
- De MM, Franceschi C, Monti D et al (2005) Inflamm-ageing and lifelong antigenic load as major determinants of ageing rate and longevity. FEBS Lett 579:2035–2039Google Scholar
- Ferrando-Martinez S, Ruiz-Mateos E, Hernandez A et al (2011) Age-related deregulation of naive T cell homeostasis in elderly humans. Age (Dordr) 33:197–207Google Scholar
- Gayoso I, Peralbo E, Sanchez-Correa B et al (2009) Phenotypic analysis of human NK cells in healthy elderly. Medimond s.r.l, Bologna, pp 105–109Google Scholar
- Gribben JG (2011) Are prognostic factors in CLL overrated? Oncology (Williston Park) 25:703–706Google Scholar
- Larbi A, Franceschi C, Mazzatti D et al (2008) Aging of the immune system as a prognostic factor for human longevity. Physiology (Bethesda) 23:64–74Google Scholar
- Lee SK, Gasser S (2010) The role of natural killer cells in cancer therapy. Front Biosci (Elite Ed) 2:380–391Google Scholar
- Myers CE, Mirza NN, Lustgarten J (2011) Immunity, cancer and aging: lessons from mouse models. Ageing Dis 2:512–523Google Scholar
- Nüssler NC, Stange BJ, Petzold M et al (2007) Reduced NK-cell activity in patients with metastatic colon cancer. Exp Clin Sci 6:1–9Google Scholar
- Remarque E, Pawelec G (1998) T cell immunosenescence and its clinical relevance in man. Rev Clin Gerontol 8:5–14Google Scholar
- Tarazona R, Gayoso I, Alonso C et al (2009) NK cells in human ageing. In: Fulop T, Franceschi C, Hirokawa K, Pawelec G (eds) Handbook on Immunosenescence. Springer, New York, pp 533–546Google Scholar