Abstract
BackgroundIndirect 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.MethodsThe 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.ResultsBoth 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.ConclusionsOur 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 registrationEudraCT #2006–002859-33.
Highlights
Indirect evidence suggesting the immunosensitivity/immunogenicity of neuroblastoma is accumulating
It has been recently reported that tumor-infiltrating T cells have prognostic value in NBL, and that combined PD-L1 and Human Leukocyte Antigens (HLA)-class I expression on tumor cells predicts the clinical outcome in NBL patients [3, 4]
In terms of possible tumor-associated antigens (TAA) for NBL, we reported that NY-ESO-1, a germ cell antigen aberrantly expressed in different tumor types, is present in NBL tumors at diagnosis
Summary
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. There is increasing evidence suggesting the immunosensitivity/immunogenicity of NBL. NBL cells express tumor-associated antigens (TAA), such as MAGE and Camisaschi et al BMC Cancer (2018) 18:983. NY-ESO-1, which are specific targets for humoral and T cell mediated response [5,6,7] Based on this experimental evidence, several ongoing clinical studies are investigating different immunological interventions such as cytokine/chemokine treatments, antibody administration, cancer vaccines and adoptive therapy with lymphocytes genetically engineered to acquire NBL specificity [8]. New clinical trials with DC loaded with NBL antigens (cell lysates, tumor RNA, TAA) are either ongoing (NCT02745756; NCT00405327) or have recently been completed (NCT01241162)
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