Interleukin-27 Acts as Multifunctional Antitumor Agent in Multiple Myeloma

Cocco, Claudia; Giuliani, Nicola; Carlo, Emma Di; Ognio, Emanuela; Storti, Paola; Abeltino, Manuela; Sorrentino, Carlo; Ponzoni, Maurilio; Ribatti, Doménico; Airoldi, Irma

doi:10.1158/1078-0432.ccr-10-0173

Cited by 83 publications

(92 citation statements)

References 51 publications

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“…[146][147][148] Similarly to IL-12, IL-27 has been shown to inhibit tumor growth and metastasis. 149 The mechanisms that drive IL-27 antitumor effects include inhibition of angiogenesis [150][151][152] and tumor cell proliferation, 153,154 and the activation of CD8 þ T and NK cells. 155,156 As IL-27 acts only on naive T cells, the concentrations of IL-27-induced pro-inflammatory cytokines are presumably not high enough to induce the appearance of adverse side effects.…”

Section: Mechanisms Of Tumor Protection Through Il-12mentioning

confidence: 99%

New insights into IL-12-mediated tumor suppression

et al. 2014

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During the past two decades, interleukin-12 (IL-12) has emerged as one of the most potent cytokines in mediating antitumor activity in a variety of preclinical models. Through pleiotropic effects on different immune cells that form the tumor microenvironment, IL-12 establishes a link between innate and adaptive immunity that involves different immune effector cells and cytokines depending on the type of tumor or the affected tissue. The robust antitumor response exerted by IL-12, however, has not yet been successfully translated into the clinics. The majority of clinical trials involving treatment with IL-12 failed to show sustained antitumor responses and were associated to toxic side effects. Here we discuss the therapeutic effects of IL-12 from preclinical to clinical studies, and will highlight promising strategies to take advantage of the antitumor activity of IL-12 while limiting adverse effects.

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Section: Mechanisms Of Tumor Protection Through Il-12mentioning

confidence: 99%

New insights into IL-12-mediated tumor suppression

et al. 2014

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“…Interestingly, IL-27 exerts opposing effects in comparison to IL-3 and IL-7. This cytokine has anti-tumor, anti-angiogenic and anabolic effect in MM, and therefore may represent a promising therapeutic agent [74].…”

Section: Pathogenesis Of Osteoblast Inhibition In MMmentioning

confidence: 99%

Bone Anabolic Agents for the Treatment of Multiple Myeloma

Vallet

2011

Cancer Microenvironment

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The majority of patients with multiple myeloma develop bone osteolytic lesions, which may lead to severe complications, including pain and fractures. The pathogenesis of bone disease depends on uncoupled bone remodeling, characterized by increased bone resorption due to upregulation of osteoclast activity and decreased bone formation due to osteoblast inhibition. In myeloma, impaired osteoblast differentiation and increased apoptosis have been described. Responsible for these effects are integrin-mediated adhesion to tumor cells and soluble factors, including WNT antagonists, BMP2 inhibitors and numerous cytokines. Based on the evidence of osteoblast suppression in myeloma, bone anabolic agents have been developed and are currently undergoing clinical evaluation. Due to bidirectional inhibitory effects characterizing tumor cells and osteoblasts interactions, agents targeting osteoblasts are expected to reduce tumor burden along with improvement of bone health. This review summarizes the current knowledge on osteoblast inhibition in myeloma and provides an overview on the clinical grade agents with bone anabolic properties, which represent new promising therapeutic strategies in myeloma.

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“…7,8 IL-27 exerts antitumor activity in different tumors through indirect 5,9-11 and direct mechanisms. 12,13 Furthermore, functional screenings of genes expressed in acute myeloid leukemia cells revealed that the IL-27R possesses hematopoietic cell-transforming properties, 14 but no information is available on the role of IL-27/IL-27R in pediatric acute lymphoblastic leukemias.…”

Section: Introductionmentioning

confidence: 99%