title: NK cell expression of natural cytotoxicity receptors may determine relapse risk in older AML patients undergoing immunotherapy for remission maintenance.
abstract: In a phase IV trial, eighty-four patients (age 18-79) with acute myeloid leukemia (AML) in first complete remission (CR) received cycles of immunotherapy with histamine dihydrochloride (HDC) and low-dose human recombinant interleukin-2 (IL-2) to prevent relapse in the post-consolidation phase. Aspects of natural killer (NK) cell biology were analyzed before and during immunotherapy with focus on outcome in older patients. In younger (<60 years old, n = 37) and older patients (>60 years old, n = 47), treatment with HDC/IL-2 resulted in an expansion of CD56(bright) and CD16+ NK cells in blood along with an increased NK cell expression of the natural cytotoxicity receptors (NCR) NKp30 and NKp46. In older patients, a high expression of NKp30 or NKp46 on CD16+ NK cells before and during therapy predicted leukemia-free and overall survival. These results suggest that NK cell functions determine relapse risk and survival in older AML patients and point to biomarkers of efficacy in protocols for remission maintenance.
authors.affiliation: TIMM Laboratory, Sahlgrenska Cancer Center, University of Gothenburg, Gothenburg 405 30, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Martner
authors.affiliation: TIMM Laboratory, Sahlgrenska Cancer Center, University of Gothenburg, Gothenburg 405 30, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Rydström
authors.affiliation: TIMM Laboratory, Sahlgrenska Cancer Center, University of Gothenburg, Gothenburg 405 30, Sweden.
authors.forename: Rebecca E
authors.initials: RE
authors.lastname: Riise
authors.affiliation: TIMM Laboratory, Sahlgrenska Cancer Center, University of Gothenburg, Gothenburg 405 30, Sweden.|Department of Hematology, University of Gothenburg, Gothenburg 413 45, Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Aurelius
authors.affiliation: Department of Hematology, University of Gothenburg, Gothenburg 413 45, Sweden.
authors.forename: Mats
authors.initials: M
authors.lastname: Brune
authors.affiliation: Department of Cellular Biotechnologies and Hematology, Sapienza University of Rome, Rome 00161, Italy.
authors.forename: Robin
authors.initials: R
authors.lastname: Foà
authors.affiliation: TIMM Laboratory, Sahlgrenska Cancer Center, University of Gothenburg, Gothenburg 405 30, Sweden.
authors.forename: Kristoffer
authors.initials: K
authors.lastname: Hellstrand
authors.affiliation: TIMM Laboratory, Sahlgrenska Cancer Center, University of Gothenburg, Gothenburg 405 30, Sweden.
authors.forename: Fredrik B
authors.initials: FB
authors.lastname: Thorén
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D019002:CD56 Antigen / Q000096:biosynthesis / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D058851:GPI-Linked Proteins / Q000096:biosynthesis / Q000276:immunology; D006632:Histamine / Q000008:administration & dosage; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D007376:Interleukin-2 / Q000008:administration & dosage / Q000031:analogs & derivatives; D053208:Kaplan-Meier Estimate; D007694:Killer Cells, Natural / Q000276:immunology*; D015470:Leukemia, Myeloid, Acute / Q000276:immunology* / Q000401:mortality / Q000628:therapy; D016131:Lymphocyte Subsets / Q000276:immunology*; D060046:Maintenance Chemotherapy / Q000379:methods; D008297:Male; D008875:Middle Aged; D055627:Natural Cytotoxicity Triggering Receptor 1 / Q000096:biosynthesis / Q000276:immunology; D055628:Natural Cytotoxicity Triggering Receptor 3 / Q000096:biosynthesis / Q000276:immunology; D009364:Neoplasm Recurrence, Local / Q000276:immunology; D017452:Receptors, IgG / Q000096:biosynthesis / Q000276:immunology; D011994:Recombinant Proteins / Q000008:administration & dosage; D012074:Remission Induction; D055815:Young Adult
chemical_list: D019002:CD56 Antigen; C428200:FCGR3B protein, human; D058851:GPI-Linked Proteins; D007376:Interleukin-2; C522918:NCAM1 protein, human; C112260:NCR1 protein, human; C431710:NCR3 protein, human; D055627:Natural Cytotoxicity Triggering Receptor 1; D055628:Natural Cytotoxicity Triggering Receptor 3; D017452:Receptors, IgG; D011994:Recombinant Proteins; D006632:Histamine; C082598:aldesleukin
keywords: Immune response; Immunity; Immunology and Microbiology Section; NKp30; NKp46; acute myeloid leukemia; immunotherapy; natural killer cells