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Published in: BMC Cancer 1/2018

Open Access 01-12-2018 | Research article

Immune landscape and in vivo immunogenicity of NY-ESO-1 tumor antigen in advanced neuroblastoma patients

Authors: Chiara Camisaschi, Salvatore Lorenzo Renne, Valeria Beretta, Francesca Rini, Rosalin Dolores Spagnuolo, Alessandra Tuccitto, Marta Giorgia Podda, Giorgio Parmiani, Licia Rivoltini, Paola Collini, Chiara Castelli, Roberto Luksch

Published in: BMC Cancer | Issue 1/2018

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Abstract

Background

Indirect evidence suggesting the immunosensitivity/immunogenicity of neuroblastoma is accumulating. The aims of this study were to investigate the immune landscape of neuroblastoma and to evaluate the in vivo immunogenicity of the NY-ESO-1 tumor antigen in advanced neuroblastoma patients.

Methods

The immune infiltrating cells of the NY-ESO-1+ tumors from three HLA*A201 patients with metastatic neuroblastoma who relapsed after conventional treatments were evaluated by immunohistochemistry. The patients were vaccinated with the HLA-A*0201-restricted peptide NY-ESO-1157-165(V). The peptide was emulsified in Montanide ISA51 and given subcutaneously in a phase I pilot study. The immunogenicity of NY-ESO-1 antigen was evaluated by monitoring mononuclear cells in patient peripheral blood, pre- and post-vaccine, by short-term in vitro sensitization, HLA-multimer staining and IFN-γ ELISpot analysis.

Results

Both CD3 T cells and CD163 myeloid cells were present in pre-vaccine tumors and PD-1 and PD-L1 expression was mainly found in the immune infiltrate. Despite the advanced stage of the disease, the vaccination induced systemic NY-ESO-1 specific CD8 T cells releasing IFN-γ in response to activation with the NY-ESO-1 peptide and an HLA-A2 positive neuroblastoma cell line.

Conclusions

Our results indicate that vaccination with a tumor-associated peptide is able to boost NY-ESO-1-specific, functionally active T cells in advanced neuroblastoma patients with lymphocyte infiltration in their pre-vaccine tumors.

Trial registration

EudraCT #2006–002859-33.
Appendix
Available only for authorised users
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Metadata
Title
Immune landscape and in vivo immunogenicity of NY-ESO-1 tumor antigen in advanced neuroblastoma patients
Authors
Chiara Camisaschi
Salvatore Lorenzo Renne
Valeria Beretta
Francesca Rini
Rosalin Dolores Spagnuolo
Alessandra Tuccitto
Marta Giorgia Podda
Giorgio Parmiani
Licia Rivoltini
Paola Collini
Chiara Castelli
Roberto Luksch
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2018
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-018-4910-8

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