title: Expansion of NK cells and reduction of NKG2D expression in chronic lymphocytic leukemia. Correlation with progressive disease.
abstract: The immune system may mediate anti-tumor responses in chronic lymphocytic leukemia (CLL) which may affect disease progression and survival. In this study, we analyzed the immune characteristics of 99 consecutive previously diagnosed CLL patients and 50 healthy controls. The distribution of lymphocyte subsets at diagnosis was retrospectively analyzed. Compared with controls, leukemia patients showed an expansion of NK and CD8 T cells at diagnosis. The relative number of CD8 T cells at diagnosis was associated with time to treatment, suggesting that CD8 T cells may modify disease progression. The distribution of lymphocyte subsets was analyzed again when patients were enrolled in this study. The median time since these patients were diagnosed was 277 weeks. Compared with diagnosis, the absolute number of CD8 T cells significantly decreased in these patients, reaching similar values to healthy controls; however NK cells kept significantly elevated overtime. Nevertheless, NK cells showed an impaired expression of NKG2D receptor and a defective cytotoxic activity. This down-regulation of NKG2D expression was further enhanced in patients with advanced and progressive disease. Additionally, membrane NKG2D levels significantly decreased on CD8 T cells, but a significant increase of NKG2D+CD4+ T cells was observed in CLL patients. The cytotoxic activity of NK cells was diminished in CLL patients; however the treatments with IL-2, IL-15, IL-21 and lenalidomide were able to restore their activity. The effect of IL-2 and IL-15 was associated with the increase of NKG2D expression on immune cells, but the effect of IL-21 and lenalidomide was not due to NKG2D up-regulation. The expansion of NK cells and the reversibility of NK cell defects provide new opportunities for the immunotherapeutic intervention in CLL.
authors.affiliation: Department of Functional Biology, Universidad de Oviedo, Oviedo, Spain; IUOPA, Universidad de Oviedo, Oviedo, Spain.
authors.forename: Leticia
authors.initials: L
authors.lastname: Huergo-Zapico
authors.affiliation: Department of Functional Biology, Universidad de Oviedo, Oviedo, Spain; IUOPA, Universidad de Oviedo, Oviedo, Spain.
authors.forename: Andrea
authors.initials: A
authors.lastname: Acebes-Huerta
authors.affiliation: Department of Hematology, Hospital Universitario Central de Asturias, Oviedo, Spain.
authors.forename: Ana Pilar
authors.initials: AP
authors.lastname: Gonzalez-Rodriguez
authors.affiliation: Department of Hematology, Hospital Cabueñes, Gijón, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Contesti
authors.affiliation: Department of Hematology, Hospital Cabueñes, Gijón, Spain.
authors.forename: Esther
authors.initials: E
authors.lastname: Gonzalez-García
authors.affiliation: Department of Hematology, Hospital Universitario Central de Asturias, Oviedo, Spain.
authors.forename: Angel R
authors.initials: AR
authors.lastname: Payer
authors.affiliation: Department of Functional Biology, Universidad de Oviedo, Oviedo, Spain; IUOPA, Universidad de Oviedo, Oviedo, Spain.
authors.forename: Monica
authors.initials: M
authors.lastname: Villa-Alvarez
authors.affiliation: Department of Functional Biology, Universidad de Oviedo, Oviedo, Spain; IUOPA, Universidad de Oviedo, Oviedo, Spain.
authors.forename: Azahara
authors.initials: A
authors.lastname: Fernández-Guizán
authors.affiliation: Department of Functional Biology, Universidad de Oviedo, Oviedo, Spain; IUOPA, Universidad de Oviedo, Oviedo, Spain.
authors.forename: Alejandro
authors.initials: A
authors.lastname: López-Soto
authors.affiliation: Department of Functional Biology, Universidad de Oviedo, Oviedo, Spain; IUOPA, Universidad de Oviedo, Oviedo, Spain.
authors.forename: Segundo
authors.initials: S
authors.lastname: Gonzalez
mesh_terms: D000368:Aged; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D018450:Disease Progression; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000175:diagnosis / Q000276:immunology* / Q000473:pathology*; D018655:Lymphocyte Count; D008297:Male; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000378:metabolism*; D011379:Prognosis
chemical_list: D007155:Immunologic Factors; D055655:NK Cell Lectin-Like Receptor Subfamily K