Antigen-Specific Immunity in Neuroblastoma Patients

Antibody and T-Cell Recognition of NY-ESO-1 Tumor Antigen

Monica Rodolfo, Roberto Luksch, Elisabeth Stockert, Yao Tseng Chen, Paola Collini, Tiziana Ranzani, Claudia Lombardo, Piero Dalerba, Licia Rivoltini, Flavio Arienti, Franca Fossati-Bellani, Lloyd J. Old, Giorgio Parmiani, Chiara Castelli

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Abstract

Neuroblastoma cells have been shown to express molecularly defined tumor-associated antigens, which could represent potential targets of T and/or B cell-mediated immunity. However, the existence of a spontaneous immune response to such tumor antigens in neuroblastoma patients has yet to be investigated. In the present work we addressed the issue of whether NY-ESO-1, a germ cell antigen aberrantly expressed in different tumor types, is expressed by neuroblastoma cells and may represent a target for humoral and/or cellular immune responses in neuroblastoma patients. We found that a large fraction of neuroblastoma biopsies, independently from the clinical stage and degree of tumor cell differentiation, expressed significant levels of NY-ESO-1 as assessed by reverse transcription-PCR and immunohistochemistry. NY-ESO-1-specific IgG antibodies were detected in the sera of 10% of neuroblastoma patients with stage III or IV disease, but not in patients in clinical remission or with earlier stages. This suggests that antibody production occurred as a late event in the course of disease. NY-ESO-1-specific immune responses were observed for CD4+ and CD8+ T cells from peripheral blood lymphocytes in 4 of 8 neuroblastoma patients, as detected by IFN-τ enzyme-linked immunospot assay after in vitro stimulation either with the NY-ESO-1 recombinant protein or with the HLA-A2-restricted peptide NY-ESO1157-167. NY-ESO-1-specific CD4+ and CD8 + T cells were also able to recognize NY-ESO-1 expressing neuroblastoma cells. The presence of T cells specific for NY-ESO-1 antigen was not associated with the stage of disease, or to the presence or absence of NY-ESO-1 specific antibodies. We conclude that NY-ESO-1 is an immunogenic antigen in neuroblastoma patients and represents a candidate target for immune-based therapy.

Original languageEnglish
Pages (from-to)6948-6955
Number of pages8
JournalCancer Research
Volume63
Issue number20
Publication statusPublished - Oct 15 2003

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Neoplasm Antigens
Neuroblastoma
Immunity
T-Lymphocytes
Antigens
Antibodies
Cellular Immunity
HLA-A2 Antigen
Enzyme-Linked Immunospot Assay
Humoral Immunity
Recombinant Proteins
Germ Cells
Reverse Transcription
Antibody Formation
Cell Differentiation
Neoplasms
B-Lymphocytes
Immunoglobulin G
Immunohistochemistry
Lymphocytes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Antigen-Specific Immunity in Neuroblastoma Patients : Antibody and T-Cell Recognition of NY-ESO-1 Tumor Antigen. / Rodolfo, Monica; Luksch, Roberto; Stockert, Elisabeth; Chen, Yao Tseng; Collini, Paola; Ranzani, Tiziana; Lombardo, Claudia; Dalerba, Piero; Rivoltini, Licia; Arienti, Flavio; Fossati-Bellani, Franca; Old, Lloyd J.; Parmiani, Giorgio; Castelli, Chiara.

In: Cancer Research, Vol. 63, No. 20, 15.10.2003, p. 6948-6955.

Research output: Contribution to journalArticle

Rodolfo, M, Luksch, R, Stockert, E, Chen, YT, Collini, P, Ranzani, T, Lombardo, C, Dalerba, P, Rivoltini, L, Arienti, F, Fossati-Bellani, F, Old, LJ, Parmiani, G & Castelli, C 2003, 'Antigen-Specific Immunity in Neuroblastoma Patients: Antibody and T-Cell Recognition of NY-ESO-1 Tumor Antigen', Cancer Research, vol. 63, no. 20, pp. 6948-6955.
Rodolfo, Monica ; Luksch, Roberto ; Stockert, Elisabeth ; Chen, Yao Tseng ; Collini, Paola ; Ranzani, Tiziana ; Lombardo, Claudia ; Dalerba, Piero ; Rivoltini, Licia ; Arienti, Flavio ; Fossati-Bellani, Franca ; Old, Lloyd J. ; Parmiani, Giorgio ; Castelli, Chiara. / Antigen-Specific Immunity in Neuroblastoma Patients : Antibody and T-Cell Recognition of NY-ESO-1 Tumor Antigen. In: Cancer Research. 2003 ; Vol. 63, No. 20. pp. 6948-6955.
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