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

Leuk Res. 2013 Apr;37(4):440-6. doi: 10.1016/j.leukres.2012.11.015. Epub 2012 Dec 20.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal / immunology
  • Antigens, CD20 / immunology*
  • B-Lymphocytes / immunology*
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Humans
  • Interleukin-8 / physiology*
  • Killer Cells, Natural / immunology*
  • Leukemia, Lymphocytic, Chronic, B-Cell / immunology*
  • Lymphocyte Depletion*
  • Receptors, IgG / agonists*

Substances

  • Antibodies, Monoclonal
  • Antigens, CD20
  • Interleukin-8
  • Receptors, IgG
  • Extracellular Signal-Regulated MAP Kinases