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, Arianna Gonelli, Giorgio Zauli

Research output: Contribution to journalArticle

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 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 CpGODN 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.

Original languageEnglish
Pages (from-to)434-437
Number of pages4
JournalJournal of Leukocyte Biology
Volume83
Issue number2
DOIs
Publication statusPublished - Feb 2 2008

Fingerprint

Oligodeoxyribonucleotides
Cell Cycle
TNF-Related Apoptosis-Inducing Ligand Receptors
Apoptosis
Death Domain Receptors
B-Cell Chronic Lymphocytic Leukemia
nutlin 3
Up-Regulation
Biomarkers

Keywords

  • Apoptosis
  • Immune activation
  • Leukemia
  • p53

ASJC Scopus subject areas

  • Cell Biology

Cite this

Combined treatment of CpG-oligodeoxynucleotide with Nutlin-3 induces strong immune stimulation coupled to cytotoxicity in B-chronic lymphocytic leukemic (B-CLL) cells. / Secchiero, Paola; Melloni, Elisabetta; Tiribelli, Mario; Gonelli, Arianna; Zauli, Giorgio.

In: Journal of Leukocyte Biology, Vol. 83, No. 2, 02.02.2008, p. 434-437.

Research output: Contribution to journalArticle

Secchiero, Paola ; Melloni, Elisabetta ; Tiribelli, Mario ; Gonelli, Arianna ; Zauli, Giorgio. / Combined treatment of CpG-oligodeoxynucleotide with Nutlin-3 induces strong immune stimulation coupled to cytotoxicity in B-chronic lymphocytic leukemic (B-CLL) cells. In: Journal of Leukocyte Biology. 2008 ; Vol. 83, No. 2. pp. 434-437.
@article{b17edcf8a0fd4cafaddb4c097ab956c6,
title = "Combined treatment of CpG-oligodeoxynucleotide with Nutlin-3 induces strong immune stimulation coupled to cytotoxicity in B-chronic lymphocytic leukemic (B-CLL) cells",
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 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 CpGODN 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.",
keywords = "Apoptosis, Immune activation, Leukemia, p53",
author = "Paola Secchiero and Elisabetta Melloni and Mario Tiribelli and Arianna Gonelli and Giorgio Zauli",
year = "2008",
month = "2",
day = "2",
doi = "10.1189/jlb.0707459",
language = "English",
volume = "83",
pages = "434--437",
journal = "Journal of Leukocyte Biology",
issn = "0741-5400",
publisher = "FASEB",
number = "2",

}

TY - JOUR

T1 - Combined treatment of CpG-oligodeoxynucleotide with Nutlin-3 induces strong immune stimulation coupled to cytotoxicity in B-chronic lymphocytic leukemic (B-CLL) cells

AU - Secchiero, Paola

AU - Melloni, Elisabetta

AU - Tiribelli, Mario

AU - Gonelli, Arianna

AU - Zauli, Giorgio

PY - 2008/2/2

Y1 - 2008/2/2

N2 - 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 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 CpGODN 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.

AB - 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 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 CpGODN 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.

KW - Apoptosis

KW - Immune activation

KW - Leukemia

KW - p53

UR - http://www.scopus.com/inward/record.url?scp=38949136279&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=38949136279&partnerID=8YFLogxK

U2 - 10.1189/jlb.0707459

DO - 10.1189/jlb.0707459

M3 - Article

C2 - 17998303

AN - SCOPUS:38949136279

VL - 83

SP - 434

EP - 437

JO - Journal of Leukocyte Biology

JF - Journal of Leukocyte Biology

SN - 0741-5400

IS - 2

ER -