Combination Therapy Using IL-2 and Anti-CD25 Results in Augmented Natural Killer Cell-Mediated Antitumor Responses

William H D Hallett, Erik Ames, Maite Álvarez, Isabel Barao, Patricia A. Taylor, Bruce R. Blazar, William J. Murphy

Research output: Contribution to journalArticle

33 Scopus citations

Abstract

Interleukin (IL)-2 has been extensively examined to promote clinical T and natural killer (NK) cell responses. Regulatory T cells (Tregs) have been shown to regulate many aspects of the immune system, including NK cell-mediated responses. We have demonstrated that in vivo administration of IL-2 led to activation and expansion of both NK cells and immunosuppressive Tregs. Therefore, we attempted to augment NK cell antitumor effects by concurrently depleting Tregs using anti-CD25. Increased NK cell activation by IL-2 was found to be correlated with an increase in classical, short-term NK cell in vitro killing assays regardless of the depletion of Tregs. But when splenocytes of the treated mice were used in long-term tumor outgrowth experiments, we observed that prior depletion of Tregs from IL-2 administration led to improved antitumor effects compared with either treatment alone. Importantly, these in vitro data are correlated with subsequent in vivo survival of leukemia-bearing mice, in which co-treatment of IL-2 with anti-CD25 led to significantly improved survival compared with mice treated with either IL-2 alone or with Treg depletion. Prior depletion of NK1.1+ cells, but not of CD8+ cells, completely abrogated all antitumor effects mediated by IL-2 and anti-CD25 combination therapy. These findings demonstrate that superior NK cell-mediated antileukemic effects can be achieved with IL-2 administration and concurrent depletion of CD25+ cells.

Original languageEnglish (US)
Pages (from-to)1088-1099
Number of pages12
JournalBiology of Blood and Marrow Transplantation
Volume14
Issue number10
DOIs
StatePublished - Oct 2008

Keywords

  • Natural killer cells
  • Regulatory T cells

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