Interleukin-23 acts as antitumor agent on childhood B-acute lymphoblastic leukemia cells

Cocco, Claudia; Canale, S; Frasson, Chiara; Carlo, Emma Di; Ognio, Emanuela; Ribatti, Doménico; Prigione, Ignazia; Basso, Giuseppe; Airoldi, Irma

doi:10.1182/blood-2009-10-248245

Cited by 44 publications

(36 citation statements)

References 47 publications

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“…21,22 Purified FL/DLBCL cells from Pt #1 --6, #8 and #12 were co-cultured with murine fibroblast NIH-3T3 transfected with pIRES-neo bicystronic plasmid vector carrying the human CD40L gene (3T3/CD40L) (kindly provided by Dr Franco Fais, Department of Experimental Medicine, University of Genova). The same cells transfected with the empty vector (3T3/empty) were used as controls.…”

Section: Subjects and Methods Patientsmentioning

confidence: 99%

“…19,20,27 Moreover, recent studies have shown that these cytokines can exert direct anti-tumor activity against solid and hematological malignancies. 17,21,22,28,29 Although the anti-tumor activity of IL-23 is quite controversial, 18,30,31 we 21 have demonstrated that IL-23 shows anti-leukemic effects by dampening directly pediatric B-acute lymphoblastic leukemia cell growth both in vitro and in vivo through the inhibition of cell proliferation and induction of apoptosis. In addition, we recently demonstrated that IL-27 acts as multifunctional anti-tumor agent in multiple myeloma (MM) 22 and inhibits acute lymphoblastic leukemia cell spreading in a pre-clinical model.…”

Section: Introductionmentioning

confidence: 97%

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Complementary IL-23 and IL-27 anti-tumor activities cause strong inhibition of human follicular and diffuse large B-cell lymphoma growth in vivo

Cocco

Carlo

Zupo³

et al. 2011

Leukemia

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Interleukin (IL)-23 and IL-27 are pro-inflammatory cytokines that share functional and structural similarities and may exert anti-tumor activities against solid and hematological malignancies. Here, we asked whether IL-23 and IL-27, alone or in combination, may act directly against human follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL) cells.In this study, we demonstrated for the first time that human primary FL and DLBCL cells expressed complete and functional IL-23 and IL-27 receptors (R) and that IL-23 and IL-27 exerted anti-tumor activities in vitro and in vivo through different and complementary mechanisms. In vivo studies using severe combined immunodeficiency /non-obese diabetic mice-injected subcutaneously with human SU-DHL-4 cell line revealed that IL-23 inhibited directly tumor-cell proliferation, whereas IL-27 impaired the angiogenic program of lymphoma cells resulting in strong reduction of cell growth. In addition, combined treatment of IL-23 and IL-27 amplified the anti-tumor effects in vivo as compared with administration of each cytokine alone. These anti-tumor mechanisms were confirmed by in vitro experiments performed with primary lymphoma cells and cell lines. Our results strongly encourage the development of future clinical trials to evaluate the toxicity and efficacy of the IL-23 and IL-27 in lymphoma patients.

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Section: Subjects and Methods Patientsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 97%

Complementary IL-23 and IL-27 anti-tumor activities cause strong inhibition of human follicular and diffuse large B-cell lymphoma growth in vivo

Cocco

Carlo

Zupo³

et al. 2011

Leukemia

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“…However, clinical trials with the anti-p40 antibody ustekinumab, which neutralizes both IL-23 and the related IL-12, have not been reproducibly effective in patients with Crohn disease (13,14). IL-23 also appears to promote tumor incidence and growth (15), but at least one report indicates that IL-23 has also anti-tumorigenic activity against pediatric B-acute lymphoblastic leukemia (B-ALL) cells (16), demonstrating (e.g. for Crohn disease and opposing roles in cancer development) that the biology of IL-23 is still incompletely understood.…”

Section: Signaling Of Interleukin 23 (Il-23) Via the Il-23 Receptor (mentioning

confidence: 99%

Identification of Canonical Tyrosine-dependent and Non-canonical Tyrosine-independent STAT3 Activation Sites in the Intracellular Domain of the Interleukin 23 Receptor

Floß

Mrotzek

Klöcker

et al. 2013

Journal of Biological Chemistry

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Background: Activation of STAT3 is the major signaling pathway of IL-23. Results:The study provides detailed characterization of IL-23-dependent signal transduction with the focus on STAT3 phosphorylation. Conclusion: Canonical tyrosine-dependent and non-canonical tyrosine-independent STAT3 activation sites are located within the IL-23R. Significance: This may be the first step in elucidating the signal transduction of IL-23, an important cytokine for T H 17 cell development.

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“…No information is available on IL-23 receptor expression and function in normal human B cells, with the only exceptions being plasma cells and early B lymphocytes (4,5). In this context, it has been shown that human plasma cells express complete IL-23 receptors and that IL-23 may modulate normal plasma cell functions (5).…”

Section: Interleukin-23mentioning

confidence: 99%

“…These cytokines are predominantly produced by antigen-presenting cells in response to microbial or host immune stimuli and are involved in the regulation of immune responses against infections and tumor development (2). Recent preclinical studies showed the direct antitumor activities of IL-12 family cytokines in different human hematologic malignancies, including pediatric acute leukemias and multiple myeloma, as well as in solid tumors (3)(4)(5)(6)(7). Here, we report and discuss recent advances in the role of IL-27 and IL-23 in multiple myeloma cells and their microenvironment and in human normal plasma cells.…”

Section: Introductionmentioning

confidence: 99%

Novel Insights into the Role of Interleukin-27 and Interleukin-23 in Human Malignant and Normal Plasma Cells

Giuliani

Airoldi

2011

Clinical Cancer Research

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Multiple myeloma is a monoclonal postgerminal center tumor that has phenotypic features of plasmablasts and/or plasma cells and usually localizes at multiple sites in the bone marrow. The pathogenesis of multiple myeloma is complex and dependent on the interactions between tumor cells and their microenvironment. Different cytokines, chemokines, and proangiogenic factors released in the tumor microenvironment are known to promote multiple myeloma cell growth. Here, we report recent advances on the role of 2 strictly related immunomodulatory cytokines, interleukin-27 (IL-27) and IL-23, in human normal and neoplastic plasma cells, highlighting their ability to (i) act directly against multiple myeloma cells, (ii) influence the multiple myeloma microenvironment by targeting osteoclast and osteoblast cells, and (iii) modulate normal plasma cell function. Finally, the therapeutic implication of these studies is discussed.

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Interleukin-23 acts as antitumor agent on childhood B-acute lymphoblastic leukemia cells

Abstract: Interleukin (IL)-

Cited by 44 publications

References 47 publications

Complementary IL-23 and IL-27 anti-tumor activities cause strong inhibition of human follicular and diffuse large B-cell lymphoma growth in vivo

Complementary IL-23 and IL-27 anti-tumor activities cause strong inhibition of human follicular and diffuse large B-cell lymphoma growth in vivo

Identification of Canonical Tyrosine-dependent and Non-canonical Tyrosine-independent STAT3 Activation Sites in the Intracellular Domain of the Interleukin 23 Receptor

Novel Insights into the Role of Interleukin-27 and Interleukin-23 in Human Malignant and Normal Plasma Cells

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