Endogenous IL-8 acts as a CD16 co-activator for natural killer-mediated anti-CD20 B cell depletion in chronic lymphocytic leukemia

• Published in: Leukemia research 2013-04, Vol.37 (4), p.440-446
• Main Authors: Laprevotte, Emilie, Ysebaert, Loïc, Klein, Christian, Valleron, Wilfried, Blanc, Amandine, Gross, Emilie, Laurent, Guy, Fournié, Jean-Jacques, Quillet-Mary, Anne
• Format: Article
• Language: English
• Subjects: ADCC; Anti-CD20 monoclonal antibodies; Antibodies, Monoclonal - immunology; Antigens, CD20 - immunology; B-Lymphocytes - immunology; Cancer; CLL; Extracellular Signal-Regulated MAP Kinases - metabolism; Hematology, Oncology and Palliative Medicine; Humans; IL-8; Immunology; Interleukin-8 - physiology; Killer Cells, Natural - immunology; Leukemia, Lymphocytic, Chronic, B-Cell - immunology; Life Sciences; Lymphocyte Depletion; Receptors, IgG - agonists
• ISSN: 0145-2126; 1873-5835; 0145-2126
• DOI: 10.1016/j.leukres.2012.11.015

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.