Expression of costimulatory molecules in human neuroblastoma. Evidence that CD40+ neuroblastoma cells undergo apoptosis following interaction with CD40L

Airoldi, Irma; Lualdi, Susanna; Bruno, Silvia; Raffaghello, Lizzia; Occhino, Marzia; Gambini, Claudio; Pistoia, Vito; Corrias, Maria Valeria

doi:10.1038/sj.bjc.6600951

Cited by 36 publications

(30 citation statements)

References 45 publications

(51 reference statements)

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“…These transfectants, which produced low amounts of the cytokine in culture supernatants, displayed dramatic reduction in their proliferation rate, increased expression of functional TNF-a binding sites, HLA and CD40 surface molecules, similarly to that observed in vitro following treatment of NB cell lines with hrIFN-g (Ponzoni et al, 1992;Montaldo et al, 1994;Airoldi et al, 2003).…”

Section: Discussionmentioning

confidence: 66%

“…ACN/IFN-g also showed enhanced CD40 gene and surface expression (Airoldi et al, 2003). ACN/IFN-g cells cocultured with parental ACN cells induced CD40 surface expression on these latter cells ( Figure 3D), further confirming that a paracrine effect was produced by the low amount of IFN-g released by the NB transfectants.…”

Section: Effect Of Ifn-c Released By Ifn-c Transfectants On Coculturementioning

confidence: 57%

“…In this respect, we have recently shown that incubation of CD40-positive NB cells with soluble or insoluble CD40L leads to tumour cell apoptosis (Airoldi et al, 2003). These observations may be relevant in the perspective of the design of a vaccination protocol for patients using allogeneic cell lines transfected with the human IFN-g gene.…”

Section: Discussionmentioning

confidence: 85%

“…We have recently demonstrated that treatment of several NB cell lines with hrIFN-g induced surface expression of CD40 (Airoldi et al, 2003). ACN/IFN-g also showed enhanced CD40 gene and surface expression (Airoldi et al, 2003).…”

Section: Effect Of Ifn-c Released By Ifn-c Transfectants On Coculturementioning

confidence: 97%

“…Furthermore, it can induce expression of functional surface CD40 molecules on NB cells (Airoldi et al, 2003), making them susceptible to CD40L-mediated apoptosis.…”

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confidence: 99%

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Low-dose interferon-γ-producing human neuroblastoma cells show reduced proliferation and delayed tumorigenicity

et al. 2004

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Interferon-g (IFN-g) directs T helper-1 cell differentiation and mediates antitumour effects in preclinical models. However, high-dose IFN-g is toxic in vivo, and IFN-g-transfected neuroblastoma (NB) cells secreting high amounts of the cytokine may be lost due to cell apoptosis or differentiation. Two human NB cell lines (ACN and SK-N-BE2(c)) differing as to genetic and phenotypic features were transfected with the human IFN-g gene and selected on the grounds of the low concentrations of IFN-g produced. In both IFN-gtransfected cell lines, autocrine and paracrine activation of IFN-g-mediated pathways occurred, leading to markedly reduced proliferation rate, to increased expression of surface HLA and CD40 molecules and of functional TNF binding sites. ACN/IFN-g cells showed a significantly delayed tumorigenicity in nude mice as compared to parental cells. ACN/IFN-g tumours were smaller, with extensive necrotic area as a result of a damaged and defective microvascular network. In addition, a significant reduction in the proliferation index was observed. This is the first demonstration that IFN-g inhibits in vivo proliferation of NB cell by acting on the tumour cell itself. This effect adds to the immunoregulatory and antiangiogenic activities operated by IFN-g in syngeneic tumourbearing hosts.

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Section: Discussionmentioning

confidence: 66%

Section: Effect Of Ifn-c Released By Ifn-c Transfectants On Coculturementioning

confidence: 57%

Section: Discussionmentioning

confidence: 85%

Section: Effect Of Ifn-c Released By Ifn-c Transfectants On Coculturementioning

confidence: 97%

“…Furthermore, it can induce expression of functional surface CD40 molecules on NB cells (Airoldi et al, 2003), making them susceptible to CD40L-mediated apoptosis.…”

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confidence: 99%

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Low-dose interferon-γ-producing human neuroblastoma cells show reduced proliferation and delayed tumorigenicity

et al. 2004

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CTLA-4 is constitutively expressed on tumor cells and can trigger apoptosis upon ligand interaction

et al. 2005

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CTLA-4 (CD152) is a cell surface receptor that behaves as a negative regulator of the proliferation and the effector function of T cells. We have previously shown that CTLA-4 is also expressed on neoplastic lymphoid and myeloid cells, and it can be targeted to induce apoptosis. In our study, we have extended our analysis and have discovered that surface expression of CTLA-4 is detectable by flow cytometry on 30 of 34 (88%)

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A transplantable TH‐MYCN transgenic tumor model in C57Bl/6 mice for preclinical immunological studies in neuroblastoma

Kroesen

Nierkens

Ansems

et al. 2013

Intl Journal of Cancer

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Current multimodal treatments for patients with neuroblastoma (NBL), including anti-disialoganglioside (GD2) monoclonal antibody (mAb) based immunotherapy, result in a favorable outcome in around only half of the patients with advanced disease. To improve this, novel immunocombinational strategies need to be developed and tested in autologous preclinical NBL models. A genetically well-explored autologous mouse model for NBL is the TH-MYCN model. However, the immunobiology of the TH-MYCN model remains largely unexplored. We developed a mouse model using a transplantable TH-MYCN cell line in syngeneic C57Bl/6 mice and characterized the immunobiology of this model. In this report, we show the relevance and opportunities of this model to study immunotherapy for human NBL. Neuroblastoma (NBL) is an extracranial solid tumor of childhood that accounts for 12% of all deaths associated with cancer in children under 15 years of age.

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Expression of costimulatory molecules in human neuroblastoma. Evidence that CD40+ neuroblastoma cells undergo apoptosis following interaction with CD40L

Cited by 36 publications

References 45 publications

Low-dose interferon-γ-producing human neuroblastoma cells show reduced proliferation and delayed tumorigenicity

Low-dose interferon-γ-producing human neuroblastoma cells show reduced proliferation and delayed tumorigenicity

CTLA-4 is constitutively expressed on tumor cells and can trigger apoptosis upon ligand interaction

A transplantable TH‐MYCN transgenic tumor model in C57Bl/6 mice for preclinical immunological studies in neuroblastoma

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