Antigen-Specific Immunity in Neuroblastoma Patients: Antibody and T-Cell Recognition of NY-ESO-1 Tumor Antigen

TY - JOUR

T1 - Antigen-Specific Immunity in Neuroblastoma Patients

T2 - Antibody and T-Cell Recognition of NY-ESO-1 Tumor Antigen

AU - Rodolfo, Monica

AU - Luksch, Roberto

AU - Stockert, Elisabeth

AU - Chen, Yao Tseng

AU - Collini, Paola

AU - Ranzani, Tiziana

AU - Lombardo, Claudia

AU - Dalerba, Piero

AU - Rivoltini, Licia

AU - Arienti, Flavio

AU - Fossati-Bellani, Franca

AU - Old, Lloyd J.

AU - Parmiani, Giorgio

AU - Castelli, Chiara

PY - 2003/10/15

Y1 - 2003/10/15

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/0142219870

M3 - Article

C2 - 14583496

SN - 0008-5472

VL - 63

SP - 6948

EP - 6955

JO - Cancer Research

JF - Cancer Research

IS - 20

ER -