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Immunogenicity of Human Neuroblastoma
Author(s) -
PRIGIONE IGNAZIA,
CORRIAS MARIA VALERIA,
AIROLDI IRMA,
RAFFAGHELLO LIZZIA,
MORANDI FABIO,
BOCCA PAOLA,
COCCO CLAUDIA,
FERRONE SOLDANO,
PISTOIA VITO
Publication year - 2004
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1322.008
Subject(s) - cd40 , immunogenicity , immunotherapy , antigen , human leukocyte antigen , biology , cancer research , immunology , antigen presentation , t cell , microbiology and biotechnology , immune system , cytotoxic t cell , in vitro , biochemistry
A bstract : 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.