Antigen-specific immunity in neuroblastoma patients: antibody and T-cell recognition of NY-ESO-1 tumor antigen.
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-gamma enzyme-linked immunospot assay after in vitro stimulation either with the NY-ESO-1 recombinant protein or with the HLA-A2-restricted peptide NY-ESO-1(157-167). 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.
Rodolfo
Monica
M
Units of Melanoma Genetics, Istituto Nazionale per lo Studio e la Cura dei Tumori, 20133 Milan, Italy. monica.rodolfo@istituotumori.mi.it
Luksch
Roberto
R
Stockert
Elisabeth
E
Chen
Yao-Tseng
YT
Collini
Paola
P
Ranzani
Tiziana
T
Lombardo
Claudia
C
Dalerba
Piero
P
Rivoltini
Licia
L
Arienti
Flavio
F
Fossati-Bellani
Franca
F
Old
Lloyd J
LJ
Parmiani
Giorgio
G
Castelli
Chiara
C
D000951:Antigens, Neoplasm; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D045744:Cell Line, Tumor; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D015789:HLA-A2 Antigen / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000097:blood; D007150:Immunohistochemistry; D008213:Lymphocyte Activation / Q000276:immunology; D008565:Membrane Proteins; D009447:Neuroblastoma / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology*
D000951:Antigens, Neoplasm; C104948:CTAG1B protein, human; D018984:Epitopes, T-Lymphocyte; D015789:HLA-A2 Antigen; D007074:Immunoglobulin G; D008565:Membrane Proteins; D010446:Peptide Fragments; D011506:Proteins