Constitutive expression of IL-12Rβ2 on human multiple myeloma cells delineates a novel therapeutic target

Airoldi, Irma; Cocco, Claudia; Giuliani, Nicola; Ferrarini, Marina; Colla, Simona; Ognio, Emanuela; Taverniti, Giuseppe; Carlo, Emma Di; Cutrona, Giovanna; Perfetti, Vittorio; Rizzoli, Vittorio; Ribatti, Doménico; Pistoia, Vito

doi:10.1182/blood-2008-02-139378

Cited by 33 publications

(42 citation statements)

References 64 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…IL-27, similar to IL-12, shows antitumor activity in different cancers through indirect mechanisms, such as induction of natural killer (NK) and CTL response or inhibition of angiogenesis, primarily due to induction of CXCL10 and CXCL9 (3,(11)(12)(13)(14). In addition, it has been reported that IL-27 directly inhibits the growth of melanoma cell lines (7) and B-acute lymphoblastic leukemia (ALL) cells expressing complete IL-27 receptor (12).…”

Section: Interleukin-27mentioning

confidence: 99%

“…Although complete IL-23 receptor is expressed in multiple myeloma cells (I. Airoldi, personal communication; ref. 3), IL-23 is ineffective in terms of modulation of multiple myeloma cell proliferation and angiogenesis, induction of apoptosis and chemotaxis, regulation of chemokine receptor expression, and cytokine production. The mechanisms underlying the lack of function of IL-23 receptor in these cells remain to be established.…”

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%

See 2 more Smart Citations

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

Giuliani

Airoldi

2011

Clinical Cancer Research

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Section: Interleukin-27mentioning

confidence: 99%

Section: Interleukin-23mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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

Giuliani

Airoldi

2011

Clinical Cancer Research

Self Cite

View full text Add to dashboard Cite

show abstract

“…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: 99%

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

View full text Add to dashboard Cite

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.

show abstract

“…IL-27 is considered a proinflammatory and an anti-inflammatory cytokine (10,11) that can inhibit TH1 (12)(13)(14), TH17 (15,16), and TH2 responses (17,18), and suppress the development of inducible regulatory T cells (19). IL-27, similarly to IL-12, shows antitumor activity in different tumors through indirect mechanisms such as induction of natural killer and CTL response or inhibition of angiogenesis primarily due to induction of CXCL10 and CXCL9 (20)(21)(22)(23)(24)(25)(26). Recently, it has been shown that IL-27 inhibits directly the proliferation of human melanoma cell lines expressing functional IL-27R (27), but there is no information on the role of IL-27 in human hematologic malignancies.…”

mentioning

confidence: 99%

Interleukin-27 Acts as Multifunctional Antitumor Agent in Multiple Myeloma

Cocco

Giuliani

Carlo

et al. 2010

Clinical Cancer Research

Self Cite

View full text Add to dashboard Cite

Purpose: Multiple myeloma (MM) derives from plasmablast/plasma cells that accumulate in the bone marrow. Different microenvironmental factors may promote metastatic dissemination especially to the skeleton, causing bone destruction. The balance between osteoclast and osteoblast activity represents a critical issue in bone remodeling. Thus, we investigated whether interluekin-27 (IL-27) may function as an antitumor agent by acting directly on MM cells and/or on osteoclasts/osteoblasts.Experimental Design: The IL-27 direct antitumor activity on MM cells was investigated in terms of angiogenesis, proliferation, apoptosis, and chemotaxis. The IL-27 activity on osteoclast/osteoblast differentiation and function was also tested. In vivo studies were done using severe combined immunodeficient/nonobese diabetic mice injected with MM cell lines. Tumors from IL-27-and PBS-treated mice were analyzed by immunohistochemistry and PCR array.Results: We showed that IL-27 (a) strongly inhibited tumor growth of primary MM cells and MM cell lines through inhibition of angiogenesis, (b) inhibited osteoclast differentiation and activity and induced osteoblast proliferation, and (c) damped in vivo tumorigenicity of human MM cell lines through inhibition of angiogenesis.Conclusions: These findings show that IL-27 may represent a novel therapeutic agent capable of inhibiting directly MM cell growth as well as osteoclast differentiation and activity. Clin Cancer Res; 16(16); 4188-97. ©2010 AACR.

show abstract

Constitutive expression of IL-12Rβ2 on human multiple myeloma cells delineates a novel therapeutic target

Cited by 33 publications

References 64 publications

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

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

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

Interleukin-27 Acts as Multifunctional Antitumor Agent in Multiple Myeloma

Contact Info

Product

Resources

About