Immunogenicity of human neuroblastoma

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

Neuroblastoma (NB) is a neuroectodermal tumor that affects children in the first years of life. Half of NB cases present with metastatic disease at diagnosis and have a poor prognosis, in spite of the most advanced chemotherapeutic protocols combined with autologous hematopoietic stem cell transplantation. Among the new avenues for NB treatment that are being explored, immunotherapy has attracted much interest. Emphasis has been placed on monoclonal antibodies directed to tumor-associated antigens-in particular the disialoganglioside GD2-that have been tested in the clinical setting with promising results. In addition, stimulation of cell-mediated antitumor effector mechanisms have been attempted-for example, by recombinant interleukin (IL)-2 administration. Nonetheless, the issue of the immunogenicity of human NB cells has never been thoroughly addressed. Here we shall review the work carried out in our lab in recent years and show that NB cells express tumor-associated antigens, such as MAGE-3, but lack constitutive expression of costimulatory molecules and surface HLA class I and II molecules. As such, NB cells are likely to be ignored by the host T cell compartment, since expression of HLA and costimulatory molecules on antigen presenting cells are sine qua non conditions for efficient peptide presentation to T cells and for the subsequent activation and clonal expansion of the latter cells. Notably, in vitro experiments with NB cell lines demonstrated that surface HLA class I molecules and the CD40 costimulatory molecule were upregulated following cell incubation with recombinant interferon-γ. Interaction of CD40 with recombinant CD40 ligand induced apoptosis of NB cells through a caspase 8-dependent mechanism. Collectively, these results indicate that the immunogenicity of human NB cells is very low but suggest that manipulation by cytokine administration or gene transfer can increase their immunogenic potential. On the other hand, NB cells represent an excellent target for natural killer cells, the potential role of which in immunotherapy of NB is now being investigated.

Original languageEnglish
Pages (from-to)69-80
Number of pages12
JournalAnnals of the New York Academy of Sciences
Volume1028
DOIs
Publication statusPublished - 2004

Fingerprint

Neuroblastoma
Molecules
Tumors
T-cells
Gene transfer
Antigens
CD40 Ligand
Caspase 8
Stem cells
Neoplasm Antigens
Interferons
Interleukin-2
Immunotherapy
Chemical activation
Monoclonal Antibodies
Cells
Apoptosis
Cytokines
Neuroectodermal Tumors
Peptides

Keywords

  • Immunotherapy
  • Neuroblastoma

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Immunogenicity of human neuroblastoma. / Prigione, Ignazia; Corrias, Maria Valeria; Airoldi, Irma; Raffaghello, Lizzia; Morandi, Fabio; Bocca, Paola; Cocco, Claudia; Ferrone, Soldano; Pistoia, Vito.

In: Annals of the New York Academy of Sciences, Vol. 1028, 2004, p. 69-80.

Research output: Contribution to journalArticle

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abstract = "Neuroblastoma (NB) is a neuroectodermal tumor that affects children in the first years of life. Half of NB cases present with metastatic disease at diagnosis and have a poor prognosis, in spite of the most advanced chemotherapeutic protocols combined with autologous hematopoietic stem cell transplantation. Among the new avenues for NB treatment that are being explored, immunotherapy has attracted much interest. Emphasis has been placed on monoclonal antibodies directed to tumor-associated antigens-in particular the disialoganglioside GD2-that have been tested in the clinical setting with promising results. In addition, stimulation of cell-mediated antitumor effector mechanisms have been attempted-for example, by recombinant interleukin (IL)-2 administration. Nonetheless, the issue of the immunogenicity of human NB cells has never been thoroughly addressed. Here we shall review the work carried out in our lab in recent years and show that NB cells express tumor-associated antigens, such as MAGE-3, but lack constitutive expression of costimulatory molecules and surface HLA class I and II molecules. As such, NB cells are likely to be ignored by the host T cell compartment, since expression of HLA and costimulatory molecules on antigen presenting cells are sine qua non conditions for efficient peptide presentation to T cells and for the subsequent activation and clonal expansion of the latter cells. Notably, in vitro experiments with NB cell lines demonstrated that surface HLA class I molecules and the CD40 costimulatory molecule were upregulated following cell incubation with recombinant interferon-γ. Interaction of CD40 with recombinant CD40 ligand induced apoptosis of NB cells through a caspase 8-dependent mechanism. Collectively, these results indicate that the immunogenicity of human NB cells is very low but suggest that manipulation by cytokine administration or gene transfer can increase their immunogenic potential. On the other hand, NB cells represent an excellent target for natural killer cells, the potential role of which in immunotherapy of NB is now being investigated.",
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