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Published online before print November 12, 2007
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© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0707459

Received for publication July 12, 2007.
Revised October 24, 2007.
Accepted for publication October 24, 2007.

Article

Combined treatment of CpG-oligodeoxynucleotide with Nutlin-3 induces strong immune stimulation coupled to cytotoxicity in B-chronic lymphocytic leukemic (B-CLL) cells

Paola Secchiero *@, Elisabetta Melloni *, Mario Tiribelli {dagger}, and Giorgio Zauli *

*Department of Morphology and Embryology, University of Ferrara, Ferrara, Italy; and {dagger}Department of Medical and Morphological Researches, Division of Hematology and Bone Marrow Transplantation, University Hospital, Udine, Italy

@ To whom correspondence should be addressed. E-mail: secchier{at}mail.umbi.umd.edu.


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Abstract

We have investigated the effect of combined treatment with CpG-oligodeoxynucleotide (CpG-ODN) plus Nutlin-3, a small molecule inhibitor of the murine double minute 2/p53 interaction, on the immune activation, cell cycle progression, and apoptosis of peripheral blood B chronic lymphocytic leukemia (B-CLL) cells. CpG-ODN induced a robust up-regulation of immune activation markers (CD54, CD69, CD80, CD86, MHC-II) in Zap70high and Zap70low B-CLL samples. Although cotreatment of B-CLL cells with CpG-ODN + Nutlin-3 did not interfere with such immune activation, CpG-ODN potentiated the Nutlin-3-mediated induction of the death receptors CD95 and TRAIL receptor 2. Importantly, treatment with CpG-ODN did not interfere with the ability of Nutlin-3 to inhibit cell cycle progression and to induce apoptosis. Thus, a therapeutic regimen including CpG-ODN plus Nutlin-3 might have the advantage to preserve the immune activation of B-CLL cells while restraining the prosurvival/proliferative potential of CpG-ODN treatment.

Key Words: leukemia • p53 • immune activation • apoptosis




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