title: Endogenous IL-8 acts as a CD16 co-activator for natural killer-mediated anti-CD20 B cell depletion in chronic lymphocytic leukemia.
abstract: Rituximab (RTX, anti-CD20 antibody) combined with chemotherapy is currently standard treatment for chronic lymphocytic leukemia (CLL). Serum level of IL-8 is a prognostic factor for CLL that correlates with disease stage. We investigated whether endogenous IL-8 affects RTX or Obinutuzumab (GA101) B-leukemic depletion mediated by natural killers (NK). Using whole peripheral blood lymphocytes from untreated CLL patients, RTX, but most significantly GA101, were effective in B-cell depletion and NK activation. IL-8 inhibition completely inhibited B-cell depletion by RTX and reduced GA101-induced B-cell depletion. Altogether results underline IL-8 as an endogenous NK co-activator and confirm GA101 therapeutic potential for CLL treatment.
authors.affiliation: INSERM UMR1037-Cancer Research Center of Toulouse, Toulouse, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Laprevotte
authors.forename: Loïc
authors.initials: L
authors.lastname: Ysebaert
authors.forename: Christian
authors.initials: C
authors.lastname: Klein
authors.forename: Wilfried
authors.initials: W
authors.lastname: Valleron
authors.forename: Amandine
authors.initials: A
authors.lastname: Blanc
authors.forename: Emilie
authors.initials: E
authors.lastname: Gross
authors.forename: Guy
authors.initials: G
authors.lastname: Laurent
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Fournié
authors.forename: Anne
authors.initials: A
authors.lastname: Quillet-Mary
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology; D018951:Antigens, CD20 / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D016209:Interleukin-8 / Q000502:physiology*; D007694:Killer Cells, Natural / Q000276:immunology*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000276:immunology*; D008212:Lymphocyte Depletion; D017452:Receptors, IgG / Q000819:agonists*
chemical_list: D000911:Antibodies, Monoclonal; D018951:Antigens, CD20; D016209:Interleukin-8; D017452:Receptors, IgG; D048049:Extracellular Signal-Regulated MAP Kinases