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Combined treatment of CpG‐oligodeoxynucleotide with Nutlin‐3 induces strong immune stimulation coupled to cytotoxicity in B‐chronic lymphocytic leukemic (B‐CLL) cells
Author(s) -
Secchiero Paola,
Melloni Elisabetta,
Tiribelli Mario,
Gonelli Arianna,
Zauli Giorgio
Publication year - 2008
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0707459
Subject(s) - cpg oligodeoxynucleotide , biology , cd80 , chronic lymphocytic leukemia , tlr9 , cancer research , immune system , cd86 , apoptosis , cpg site , immunology , t cell , microbiology and biotechnology , leukemia , cytotoxic t cell , cd40 , dna methylation , biochemistry , gene expression , gene , in vitro
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 Zap70 high and Zap70 low 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.