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

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

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)983
JournalBMC Cancer
Volume18
Issue number1
DOIs
Publication statusPublished - Oct 16 2018

Keywords

  • Antigens, Neoplasm/immunology
  • Cancer Vaccines
  • Child, Preschool
  • Female
  • Humans
  • Immunogenicity, Vaccine
  • Immunotherapy, Active
  • Lymphocytes, Tumor-Infiltrating/immunology
  • Membrane Proteins/immunology
  • Neuroblastoma/immunology
  • T-Lymphocyte Subsets/immunology

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