Irma Airoldi

Università degli studi di Parma, Parma, Emilia-Romagna, Italy

Are you Irma Airoldi?

Claim your profile

Publications (64)414.43 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Different cytokines play crucial roles in inflammation and in polarizing immune responses, including IL-27 that exerts pro- and anti-inflammatory functions. Although the activity of IL-27 is well characterized in murine immune cells, only limited information is available regarding the natural cellular sources of IL-27 in humans and its effects on human immune cells. Dendritic cells (DCs) are the most potent professional APCs that in the immature state are positioned throughout peripheral tissues by acting as sentinels, sensing the presence of Ags. Activated DCs migrate into the lymph nodes and direct Ag-specific T cell responses, thus acting as key players in both adaptive and innate immunity. In this study we asked whether IL-27 is produced by human secondary lymphoid organs and what is its functional role on human DCs. To our knowledge, we provide the first evidence that 1) in lymph nodes, macrophages are the major source for IL-27; 2) immature and mature human DCs express functional IL-27R; 3) IL-27 exerts immunosuppressive activity by crippling the Ag processing machinery in immature DCs under steady-state conditions and after pulsing with a viral Ag; and 4) IL-27 is chemotactic for human DCs. Our findings highlight novel mechanisms underlying the immunosuppressive activity of IL-27, suggesting that this cytokine may function as a homeostatic cytokine in secondary lymphoid organs by limiting duration and/or intensity of ongoing adaptive immune responses. The results presented in this study pave the way to future studies aimed at investigating whether dysregulation of IL-27 expression and function may be involved in pathogenesis of autoimmune disease and cancer.
    The Journal of Immunology 02/2014; · 5.52 Impact Factor
  • Source
    Fabio Morandi, Irma Airoldi, Vito Pistoia
    [Show abstract] [Hide abstract]
    ABSTRACT: HLA-G and HLA-E are HLA-Ib molecules with several immunoregulatory properties. Their cell surface expression can be modulated by different cytokines. Since IL-27 and IL-30 may either stimulate or regulate immune responses, we have here tested whether these cytokines may modulate HLA-G and -E expression and function on human monocytes. Monocytes expressed gp130 and WSX-1, the two chains of IL27 receptor (R), and IL6Rα (that serves as IL-30R, in combination with gp130). However, only IL27R appeared to be functional, as witnessed by IL-27 driven STAT1/ STAT3 phosphorylation. IL-27, but not IL-30, significantly upregulated HLA-E (but not HLA-G) expression on monocytes. IFN-γ; secretion by activated NK cells was dampened when the latter cells were cocultured with IL-27 pretreated autologous monocytes. Such effect was not achieved using untreated or IL-30 pretreated monocytes, thus indicating that IL-27 driven HLA-E upregulation might be involved, possibly through the interaction of this molecule with CD94/NKG2A inhibitory receptor on NK cells. In contrast, cytotoxic granules release by NK cell in response to K562 cells was unaffected in the presence of IL-27 pretreated monocytes. In conclusion, we delineated a novel immunoregulatory function of IL-27 involving HLA-E upregulation on monocytes that might in turn indirectly impair some NK cell functions.
    Journal of Immunology Research 01/2014; 2014:938561. · 2.93 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Prostate cancer (PCa) is of increasing significance worldwide as a consequence of the population ageing. Fragile elderly patients may particularly benefit from noninvasive and well tolerable immunotherapeutic approaches. Preclinical studies have revealed that the immune-regulatory cytokine IL-27 may exert anti-tumor activities in a variety of tumor types without discernable toxicity. We, thus, investigated whether IL-27 may function as anti-tumor agent in human (h) PCa and analyzed the rationale for its clinical application. In vitro, IL-27 treatment significantly inhibited proliferation and reduced the angiogenic potential of hPCa cells by down-regulating the pro-angiogenesis-related genes fms-related tyrosine kinase (FLT)1, prostaglandin G/H synthase 1/cyclooxygenase-1 (PTGS1/COX-1) and fibroblast growth factor receptor (FGFR)3. In addition, IL-27 up-regulated the anti-angiogenesis-related genes such as CXCL10 and TIMP metallopeptidase inhibitor 3 (TIMP3). In vivo, IL-27 reduced proliferation and vascularization in association with ischemic necrosis of tumors developed after PC3 or DU145 cell injection in athymic nude mice. In patients' prostate tissues, IL-27R was expressed by normal epithelia and low grade PCa and lost by high tumor grade and stages. Nevertheless, IL-27R was expressed by CD11c+, CD4+ and CD8+ leukocytes infiltrating the tumor and draining lymph nodes. These data lead to the conclusion that i) IL-27's anti-PCa potential may be fully exploited in patients with well-differentiated, localized IL-27R positive PCa, since in this case it may act on both cancerous epithelia and the tumor microenvironment; ii) PCa patients bearing high grade and stage tumor that lack IL-27R may benefit, however, from IL-27's immune-stimulatory properties.
    Oncotarget 12/2013; · 6.64 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The IL-27 cytokine subunit p28, also called IL-30, has been recognized as novel immunoregulatory mediator endowed with its own functions. These are currently the subject of discussion in immunology, but completely unexplored in cancer biology. We set out to investigate IL-30's role in prostate carcinogenesis and its effects on human (h) prostate cancer (PCa) cells. IL-30 expression, as visualized by immunohistochemistry and real-time RT-PCR on prostate and draining lymph nodes from 125 PCa patients, was correlated with clinico-pathological data. IL-30 regulation of hPCa cell viability and expression of selected gene clusters was tested by flow cytometry and PCR Array. IL-30, absent in normal prostatic epithelia, was expressed by cancerous epithelia with Gleason ≥7 of 21.3% of PCa stage I-III and 40.9% of PCa stage IV. IL-30 expression by Tumor Infiltrating Leukocytes (T-ILK) was higher in stage IV that in stage I-III PCa (P=0.0006) or in control tissue (P=0.0011). IL-30 expression in prostate draining Lymph Nodes (LN)-ILK was higher in stage IV than in stage I-III PCa (P=0.0031) or in control nodes (P=0.0023). The main IL-30 sources were identified as CD68+macrophages, CD33+/CD11b+myeloid cells and CD14+monocytes. In vitro, IL-30 stimulated proliferation of hPCa cells and also down-regulated CCL16/LEC, TNFSF14/LIGHT, Chemokine-like-factor/CKLF and particularly CKLF-like MARVEL transmembrane-domain-containing-3/CMTM3 and greatly up-regulated ChemR23/CMKLR. We provide the first evidence that IL-30 is implicated in PCa progression since I) its expression by PCa or T- and LN-ILK correlates with advanced disease grade and stage, and II) IL-30 exerts pro-tumor activity in hPCa cells.
    Clinical Cancer Research 11/2013; · 7.84 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Interleukin (IL)-18 is an immune-enhancing cytokine, which induces Interferon (IFN)-γ production, Th1-responses and anti-tumor effects. In turn, IFN-γ stimulates IL-18 Binding Protein (BP) production, which blocks IL-18 activity. In view of the potential use of IL-18 in epithelial ovarian cancer (EOC) immunotherapy, here we studied IL-18BP expression and its regulation by cytokines in EOC cells in vitro and in vivo. Expression and production of IL-18BP in EOC cell lines, primary ovarian carcinomas and the corresponding normal tissues, patients' serum and ascites were investigated by immunochemistry, ELISA, screening of gene expression profiles and RT-PCR. Analysis of gene expression profiles revealed that IL18BP mRNA is increased in EOC tumors compared to normal ovary cells. Release of IL-18BP was detectable in EOC sera and at greater extent in the ascites, indicating production at the tumor site. Indeed, immunochemical analyses on cells isolated from the ascites and on tumor sections indicated that IL-18BP is expressed in both tumor cells and tumor-associated leukocytes, which displayed a CD3-CD20-NKp46-CD13+CD14low phenotype. EOC cell lines do not constitutively express IL-18BP. However, its release is inducible both by IFN-γ stimulation in vitro and by xenotransplantation of EOC cells in immune-deficient mice, suggesting a role for the microenvironment. In vitro experiments and immunochemistry indicated that also IL-27 is involved in IL-18BP up-regulation in EOC cell lines and primary cells through STAT1 activation. Altogether these data indicate that IL-18BP, which is produced in EOC in response to micro-environmental factors, may inhibit endogenous or exogenous IL-18 activity.
    Clinical Cancer Research 07/2013; · 7.84 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Hypoxia-inducible transcription factor-1 (HIF-1α) is overexpressed in multiple myeloma (MM) cells within the hypoxic microenvironment. Herein we explored the effect of persistent HIF-1α inhibition by a lentivirus shRNA pool on MM cell growth either in vitro or in vivo and on the transcriptional and pro-angiogenic profiles of MM cells. HIF-1α suppression did not have a significant impact on MM cell proliferation and survival in vitro although increased the anti-proliferative effect of lenalidomide. On the other hand we found that HIF-1α inhibition in MM cells down-regulates the pro-angiogenic genes VEGF, IL8, IL10, CCL2, CCL5 and MMP9. Pro-osteoclastogenic cytokines were also inhibited, such as IL-7 and CCL3/MIP-1α. The effect of HIF-1α inhibition was assessed in vivo in NOD/SCID mice both in a subcutaneous and an intratibial MM model. HIF-1α inhibition caused a dramatic reduction in the weight and volume of the tumor burden in both mouse models. Moreover, a significant reduction of the number of vessels and VEGF immunostaining was observed. Finally, in the intra-tibial experiments HIF-1α inhibition significantly blocked bone destruction. Overall our data indicate that HIF-1α suppression in MM cells significantly blocks MM-induced angiogenesis and reduces MM tumor burden and bone destruction in vivo, supporting HIF-1α as a potential therapeutic target in MM.Leukemia accepted article preview online, 24 January 2013; doi:10.1038/leu.2013.24.
    Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 01/2013; · 10.16 Impact Factor
  • Source
  • Claudia Cocco, Irma Airoldi
    Immunotherapy 07/2012; 4(7):667-8. · 2.39 Impact Factor
  • Claudia Cocco, Irma Airoldi
    Immunotherapy 07/2012; 4(7):669-70. · 2.39 Impact Factor
  • Claudia Cocco, Irma Airoldi
    Immunotherapy 07/2012; 4(7):668. · 2.39 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: IL-27 and TCRγδ(+) T lymphocytes play critical roles in both innate and adaptive immune responses in health and disease, including infection and tumors. Although the activity of IL-27 is well characterized in different human immune cells, no information is available on the role of IL-27 in human TCRγδ(+) T lymphocytes. Here, we provide the first evidence that TCRγδ(+) T lymphocytes express both gp130 and WSX-1 chains of IL-27R, and that IL-27 may function in TCRγδ(+) T cells by (i) inducing STAT1 and STAT3 phosphorylation, (ii) stimulating cytotoxicity against tumor cells through upregulation of cytotoxic granules production, (iii) reducing the release of Th2-related cytokines, such as IL-5 and IL-13, and inducing IFN-γ production, and (iv) upregulating the expression of CD62L. These results highlighted a novel immunoregulatory property of human IL-27 that may be relevant in the immune response against tumors. Our results may offer new perspectives for the development of future clinical trials using IL-27 and TCRγδ(+) cells for cancer immunotherapy.
    European Journal of Immunology 06/2012; 42(6):1547-52. · 4.97 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: AML is a hematologic malignancy that represents 15-20% of all childhood acute leukemias and is responsible for more than one-half of pediatric leukemic deaths. The bulk tumor is continuously regenerated and sustained by rare leukemic ICs that proliferate slowly, thus resulting refractory to chemotherapeutic agents targeting highly proliferating cells within the tumor. Therefore, a complete eradication of the bulk tumor may depend on efficacy of therapies that target IC. In spite of the improvements in the treatment of AML, the difficulty to eradicate completely the disease incites research for innovative therapeutic approaches. In this regard, the role of cytokines in the treatment of AML has been investigated for many years, and some of them have been tested in clinical trials as a result of their immunomodulatory properties. Furthermore, recent preclinical studies highlighted the ability of the IL-12 superfamily cytokines as potent antileukemic agents that act directly on tumor cells and on leukemic IC, thus opening new perspectives for leukemic patient treatment. Here, we review the current knowledge about the antileukemic effects of cytokines, documented in preclinical and clinical studies, discussing their potential clinical application.
    Journal of leukocyte biology 05/2012; 92(3):567-75. · 4.99 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Acute myeloid leukemia (AML) accounts for more than half of fatal cases in all pediatric leukemia patients; this observation highlights the need of more effective therapies. Thus, we investigated whether interleukin (IL)-27, an immunomodulatory cytokine, functions as an antitumor agent against pediatric AML cells. Expression of WSX-1 and gp130 on AML cells from 16 pediatric patients was studied by flow cytometry. Modulation of leukemia cell proliferation or apoptosis upon IL-27 treatment in vitro was tested by bromodeoxyuridine/propidium iodide (PI) and Ki67, or Annexin V/PI staining and flow cytometric analysis. The angiogenic potential of AML cells treated or not with IL-27 was studied by chorioallantoic membrane assay and PCR array. In vivo studies were carried out using nonobese diabetic/severe combined immunodeficient (NOD/SCID)/Il2rg(-/-) mice injected intravenously with five pediatric AML cell samples. Leukemic cells engrafted in PBS and IL-27-treated animals were studied by immunohistochemical/morphologic analysis and by PCR array for expression angiogenic/dissemination-related genes. We provided the first demonstration that (i) AML cells injected into NOD/SCID/Il2rg(-/-) mice gave rise to leukemia dissemination that was severely hampered by IL-27, (ii) compared with controls, leukemia cells harvested from IL-27-treated mice showed significant reduction of their angiogenic and spreading related genes, and (iii) similarly to what was observed in vivo, IL-27 reduced in vitro AML cell proliferation and modulated the expression of different genes involved in the angiogenic/spreading process. These results provide an experimental rationale for the development of future clinical trials aimed at evaluating the toxicity and efficacy of IL-27.
    Clinical Cancer Research 03/2012; 18(6):1630-40. · 7.84 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Uveal melanoma is an aggressive cancer that metastasizes to the liver in about half of the patients, with a high lethality rate. Identification of patients at high risk of metastases may provide indication for a frequent follow-up for early detection of metastases and treatment. The analysis of the gene expression profiles of primary human uveal melanomas showed high expression of SDCBP gene (encoding for syndecan-binding protein-1 or mda-9/syntenin), which appeared higher in patients with recurrence, whereas expression of syndecans was lower and unrelated to progression. Moreover, we found that high expression of SDCBP gene was related to metastatic progression in two additional independent datasets of uveal melanoma patients. More importantly, immunohistochemistry showed that high expression of mda-9/syntenin protein in primary tumors was significantly related to metastatic recurrence in our cohort of patients. Mda-9/syntenin expression was confirmed by RT-PCR, immunofluorescence and immunohistochemistry in cultured uveal melanoma cells or primary tumors. Interestingly, mda-9/syntenin showed both cytoplasmic and nuclear localization in cell lines and in a fraction of patients, suggesting its possible involvement in nuclear functions. A pseudo-metastatic model of uveal melanoma to the liver was developed in NOD/SCID/IL2Rγ null mice and the study of mda-9/syntenin expression in primary and metastatic lesions revealed higher mda-9/syntenin in metastases. The inhibition of SDCBP expression by siRNA impaired the ability of uveal melanoma cells to migrate in a wound-healing assay. Moreover, silencing of SDCBP in mda-9/syntenin-high uveal melanoma cells inhibited the hepatocyte growth factor (HGF)-triggered invasion of matrigel membranes and inhibited the activation of FAK, AKT and Src. Conversely syntenin overexpression in mda-9/syntenin-low uveal melanoma cells mediated opposite effects. These results suggest that mda-9/syntenin is involved in uveal melanoma progression and that it warrants further investigation as a candidate molecular marker of metastases and a potential therapeutic target.
    PLoS ONE 01/2012; 7(1):e29989. · 3.53 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Abstract 2947 It has been previously reported that bone marrow (BM) microenvironment is hypoxic in multiple myeloma (MM) patients and that hypoxia inducible factor (HIF)-1 is overexpressed by MM cells. However, the potential role of HIF-1 as a therapeutic target in MM is not known and is currently under investigation. In this study we explored the effect of persistent HIF-1 inhibition by expression of a lentivirus shRNA pool in MM cells on proliferation, survival and transcriptional and pro-angiogenic profiles of MM cells either in vitro or in vivo in mouse models. A HIF-1 Lentivirus shRNA pool was used for HIF-1 stable knock-down in human myeloma cell lines (HMCL)s and the pKLO.1 lentiviral vector was used as the empty control vector. HMCLs were infected and then selected with puromycin. Selected clones were screened for HIF-1, HIF-1beta, HIF-2 and HIF-3. The transcriptional profiles were evaluated in the HMCL JJN3 cells transduced with shRNA forHIF-1 (JJN3-anti-HIF-1) and on those infected with the control vector pKLO.1 (JJN3-pKLO.1) by U133 Plus2.0 Arrays (Affymetrix(R)) either in hypoxic or normoxic conditions. Microarray data were further validated by quantitative real time PCR and by ELISA assays for protein levels. Finally the effect of HIF-1 inhibition in MM cells was assessed in vivo in NOD/SCID mice both in subcutaneous and intratibial models. Together with tumor volume and weight, microvascular density was evaluated by CD34 immunostaining. Cortical bone thickness was determined by microQcT in the intratibial mouse model. Among the genes significantly modulated by HIF-1 inhibition (327 and 361 genes in hypoxic and normoxic condition, respectively), we found that the pro-angiogenic molecules VEGF, IL8, IL10, CCL2, CCL5, MMP9 were down-regulated by HIF-1 inhibition. Interestingly some pro-osteoclastogenic cytokines were also inhibited including IL-7 and CCL3/MIP-1. In the in vivo mouse models, we found that mice, injected either subcutaneously or intratibially with JJN3-anti-HIF-1, showed a dramatic reduction in the weight and volume of the tumor burden compared to mice inoculated with the JJN3-pKLO.1. A significant reduction in the number of vessels X field and VEGF immunostaining were observed in both mouse models. Moreover in the intratibial experiments HIF-1 inhibition significantly blocked MM-induced bone destruction. Overall our data indicate that HIF-1 suppression in myeloma cells significantly blocks MM-induced angiogenesis and reduces the MM tumor burden and bone destruction in vivo suggesting that HIF-1 is a potential therapeutic target in MM. DisclosuresNo relevant conflicts of interest to declare.
    ASH Annual Meeting Abstracts. 01/2012; 120(21):2947.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: 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.
    Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 12/2011; 26(6):1365-74. · 10.16 Impact Factor
  • Claudia Cocco, Vito Pistoia, Irma Airoldi
    [Show abstract] [Hide abstract]
    ABSTRACT: B acute lymphoblastic leukemia (ALL) is the most common pediatric hematologic malignancy. Although patient cure has reached an excellent rate, a minority of cases relapse and need novel therapies. IL-12, IL-23 and IL-27 belong to the IL-12 superfamily and exert immunological and anti-tumor functions. The latter can be mediated by activation of immune responses or by the direct activity on cancer cells. Recently, the role of IL-12, IL-23 and IL-27 in the control of pediatric B-ALL has been unveiled. Here, we discuss in a translational perspective the role of IL-12 family cytokines in pediatric B-ALL, highlighting similarities and differences in their mechanisms of action.
    Critical reviews in oncology/hematology 12/2011; 83(3):310-8. · 5.27 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The role of angiogenesis in haematological malignancies has been recently recognized. In these tumors, angiogenesis has been investigated predominantly in the bone marrow (BM) compartment where it appears to be regulated by multiple interactions between malignant cells and different cell populations present in the tumor microenvironment. Thus, angiogenesis represents a therapeutic target that opens new perspectives for the treatment of haematological malignancies. Cytokines are small proteins that mediate intercellular communications, thus regulating important cellular functions, such as immune responses and angiogenesis. Some cytokines show anti-angiogenic properties through different mechanisms; these cytokines can interfere directly with biological functions of endothelial cells and/or target tumor cells inhibiting their capability to stimulate formation of new microvessels that are essential for tumor growth and dissemination. In this review we will summarize the current knowledge about the role of cytokines as anti-angiogenic agents in cancer, focusing our attention on the anti-angiogenic activity of IL-12 family members in haematological malignancies.
    Current cancer drug targets 09/2011; 11(9):997-1004. · 5.13 Impact Factor
  • Nicola Giuliani, Irma Airoldi
    [Show abstract] [Hide abstract]
    ABSTRACT: 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.
    Clinical Cancer Research 08/2011; 17(22):6963-70. · 7.84 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Childhood acute myeloid leukemia (AML) is a hematological malignancy in which tumor burden is continuously replenished by leukemic-initiating cells (ICs), which proliferate slowly and are refractory to chemotherapeutic agents. We investigated whether interleukin (IL)-12, an immuno-modulatory cytokine with anti-tumor activity, may target AML blasts (CD45(+)CD33(+)) and populations known to contain leukemia ICs (that is, CD34(+)CD38(-), CD33(+)CD38(+) and CD44(+)CD38(-) cells). We demonstrate for the first time that: i) AML blasts and their CD34(+)CD38(-), CD33(+)CD38(+), CD44(+)CD38(-) subsets express the heterodimeric IL-12 receptor (IL-12R), ii) AML cells injected subcutaneously into NOD/SCID/Il2rg(-/-) (NSG) mice developed a localized tumor mass containing leukemic ICs and blasts that were virtually eliminated by IL-12 treatment, iii) AML cells injected intravenously into NSG mice engrafted within the first month in the spleen, but not in bone marrow or peripheral blood. At this time, IL-12 dramatically dampened AML CD45(+)CD33(+), CD34(+)CD38(-), CD33(+)CD38(+) and CD44(+)CD38(-) populations, only sparing residual CD33(+)CD38(+) cells that did not express IL-12Rβ2. From 30 to 60 days after the initial inoculum, these IL-12-unresponsive cells expanded and metastasized in both control and IL-12-treated NSG mice. Our data indicate that the absence of IL-12Rβ2 in pediatric AML cells favours leukemia progression in NOD/SCID/IL2Rγc-deficient mice.
    Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 08/2011; 26(2):225-35. · 10.16 Impact Factor

Publication Stats

805 Citations
414.43 Total Impact Points

Institutions

  • 2010–2013
    • Università degli studi di Parma
      • Department of Clinical and Experimental Medicine
      Parma, Emilia-Romagna, Italy
  • 1997–2013
    • IRCCS Istituto G. Gaslini
      • Department of Experimental and Laboratory Medicine
      Genova, Liguria, Italy