title: Targeting NK-cell checkpoints for cancer immunotherapy.
abstract: Natural Killer (NK) cells are cytotoxic lymphocytes specialized in early defense against virus-infected and transformed cells. NK-cell function is regulated by activating and inhibitory surface receptors recognizing their ligands on transformed cells. Modulation of NK numbers and/or function by a variety of agents such as cytokines and monoclonal antibodies may result in enhanced anti-tumor activity. Recombinant cytokines (i.e., IL-15 and IL-2), antibodies blocking inhibitory receptors (i.e., KIR, NKG2A and TIGIT) and agonists delivering signals via CD137, NKG2D and CD16 stand out as the most suitable opportunities. These agents can be used to potentiate NKcell- mediated antibody-dependent cellular cytotoxicity (ADCC) against antibody-coated tumor cells, offering potential for multiple combinatorial immunotherapy strategies against cancer.
authors.affiliation: Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain.
authors.forename: Aura
authors.initials: A
authors.lastname: Muntasell
authors.affiliation: Centro de Investigacion Medica Aplicada (CIMA), Pamplona, Spain.
authors.forename: Maria C
authors.initials: MC
authors.lastname: Ochoa
authors.affiliation: Centro de Investigacion Medica Aplicada (CIMA), Pamplona, Spain.
authors.forename: Luna
authors.initials: L
authors.lastname: Cordeiro
authors.affiliation: Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain.
authors.forename: Pedro
authors.initials: P
authors.lastname: Berraondo
authors.affiliation: Departamento de Inmunologia e Inmunoterapia, Clinica Universidad de Navarra, Pamplona, Spain.
authors.forename: Ascension
authors.initials: A
authors.lastname: López-Díaz de Cerio
authors.affiliation: Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain.
authors.forename: Mariona
authors.initials: M
authors.lastname: Cabo
authors.affiliation: Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: López-Botet
authors.affiliation: Centro de Investigacion Medica Aplicada (CIMA), Pamplona, Spain; Departamento de Inmunologia e Inmunoterapia, Clinica Universidad de Navarra, Pamplona, Spain; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Spain. Electronic address: imelero@unav.es.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Melero
mesh_terms: D000912:Antibodies, Neoplasm / Q000627:therapeutic use*; D000920:Antibody-Dependent Cell Cytotoxicity / Q000187:drug effects; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D019409:Interleukin-15 / Q000627:therapeutic use*; D007376:Interleukin-2 / Q000627:therapeutic use*; D007694:Killer Cells, Natural / Q000276:immunology* / Q000473:pathology; D009369:Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors / Q000276:immunology; D011994:Recombinant Proteins / Q000627:therapeutic use
chemical_list: D000912:Antibodies, Neoplasm; C569274:IL15 protein, human; C508594:IL2 protein, human; D019409:Interleukin-15; D007376:Interleukin-2; D011971:Receptors, Immunologic; D011994:Recombinant Proteins