title: Immunosenescence: limitations of natural killer cell-based cancer immunotherapy.
abstract: Cancer is primarily considered a disease of old age. Immunosenescence refers to the age-associated changes in the immune system, and its contribution to the increased risk of cancer in old individuals has been discussed for many years. Natural killer (NK) cells are cytotoxic innate immune cells specialized in defence against tumour and virus-infected cells. NK cell cytotoxicity is the result of a fine balance between activating and inhibitory receptors. Several activating receptors have been identified that recognize different ligands frequently found over-expressed on tumour cells or virus-infected cells. The most important NK cell inhibitory receptors interact with major histocompatibility complex class I molecules expressed on almost all nucleated cells preventing NK cell-mediated lysis of healthy cells. NK cell immunosenescence is characterized by a redistribution of NK cell subsets, a diminished expression of several activating receptors and lower per-cell cytotoxicity. Altered expression of activating receptors has also been described in young and elderly cancer patients probably due to chronic exposure to ligands on tumour cells. Thus, the effect of both age and cancer may act synergistically to diminish NK cell-mediated tumour immunosurveillance. Different strategies harnessing the power of NK cells to target tumour cells have been designed including adoptive therapy with autologous or allogeneic expanded NK cells. In addition, checkpoint blockade of inhibitory receptors and the use of agonist antibodies to stimulate activating receptors are emerging areas of research. In this context, the effect of immunosenescence should be considered to improve the efficiency of cancer immunotherapy.
authors.affiliation: Immunology Unit, University of Extremadura, Cáceres, Spain.
authors.forename: Raquel
authors.initials: R
authors.lastname: Tarazona
authors.affiliation: Immunology Unit, University of Extremadura, Cáceres, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Sanchez-Correa
authors.affiliation: Department of Haematology, Hospital San Pedro de Alcantara, Cáceres, Spain.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Casas-Avilés
authors.affiliation: IMIBIC - Reina Sofia University Hospital - University of Cordoba, REIPI, Córdoba, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Campos
authors.affiliation: IMIBIC - Reina Sofia University Hospital - University of Cordoba, REIPI, Córdoba, Spain.|Brighton and Sussex Medical School, University of Sussex, Brighton, UK.
authors.forename: Alejandra
authors.initials: A
authors.lastname: Pera
authors.affiliation: Immunology Unit, University of Extremadura, Cáceres, Spain.
authors.forename: Sara
authors.initials: S
authors.lastname: Morgado
authors.affiliation: IMIBIC - Reina Sofia University Hospital - University of Cordoba, REIPI, Córdoba, Spain.
authors.forename: Nelson
authors.initials: N
authors.lastname: López-Sejas
authors.affiliation: IMIBIC - Reina Sofia University Hospital - University of Cordoba, REIPI, Córdoba, Spain.
authors.forename: Fakhri
authors.initials: F
authors.lastname: Hassouneh
authors.affiliation: Department of Haematology, Hospital San Pedro de Alcantara, Cáceres, Spain.
authors.forename: Juan M
authors.initials: JM
authors.lastname: Bergua
authors.affiliation: Department of Haematology, Hospital San Pedro de Alcantara, Cáceres, Spain.
authors.forename: Maria Jose
authors.initials: MJ
authors.lastname: Arcos
authors.affiliation: Department of Haematology, Hospital San Pedro de Alcantara, Cáceres, Spain.
authors.forename: Helena
authors.initials: H
authors.lastname: Bañas
authors.affiliation: Immunology Unit, University of Extremadura, Cáceres, Spain.|Stem Cell Therapy Unit, Minimally Invasive Surgery Centre Jesus Uson, Cáceres, Spain.
authors.forename: Javier G
authors.initials: JG
authors.lastname: Casado
authors.affiliation: Histology and Pathology Unit, Faculty of Veterinary, University of Extremadura, Cáceres, Spain.
authors.forename: Esther
authors.initials: E
authors.lastname: Durán
authors.affiliation: IMIBIC - Reina Sofia University Hospital - University of Cordoba, REIPI, Córdoba, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Labella
authors.affiliation: IMIBIC - Reina Sofia University Hospital - University of Cordoba, REIPI, Córdoba, Spain. rsolana@uco.es.|Department of Immunology, Facultad de Medicina Universidad de Córdoba, Avenida de Menéndez Pidal s/n, 14004, Córdoba, Spain. rsolana@uco.es.
authors.forename: Rafael
authors.initials: R
authors.lastname: Solana
mesh_terms: D000818:Animals; D006801:Humans; D000068884:Immunosenescence / Q000276:immunology*; D016219:Immunotherapy, Adoptive / Q000379:methods*; D007694:Killer Cells, Natural / Q000276:immunology*; D008024:Ligands; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy*
chemical_list: D008024:Ligands
keywords: Ageing; Cancer immunotherapy; Checkpoint blockade; NK cell immunosenescence; PIVAC 15