TY - JOUR
T1 - Immune landscape and in vivo immunogenicity of NY-ESO-1 tumor antigen in advanced neuroblastoma patients
AU - Camisaschi, Chiara
AU - Renne, Salvatore Lorenzo
AU - Beretta, Valeria
AU - Rini, Francesca
AU - Spagnuolo, Rosalin Dolores
AU - Tuccitto, Alessandra
AU - Podda, Marta Giorgia
AU - Parmiani, Giorgio
AU - Rivoltini, Licia
AU - Collini, Paola
AU - Castelli, Chiara
AU - Luksch, Roberto
PY - 2018/10/16
Y1 - 2018/10/16
N2 - 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.
AB - 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.
KW - Antigens, Neoplasm/immunology
KW - Cancer Vaccines
KW - Child, Preschool
KW - Female
KW - Humans
KW - Immunogenicity, Vaccine
KW - Immunotherapy, Active
KW - Lymphocytes, Tumor-Infiltrating/immunology
KW - Membrane Proteins/immunology
KW - Neuroblastoma/immunology
KW - T-Lymphocyte Subsets/immunology
U2 - 10.1186/s12885-018-4910-8
DO - 10.1186/s12885-018-4910-8
M3 - Article
C2 - 30326856
VL - 18
SP - 983
JO - BMC Cancer
JF - BMC Cancer
SN - 1471-2407
IS - 1
ER -