Article: article from journal or magazin.
Naturally occurring human lymphocyte antigen-A2 restricted CD8+ T-cell response to the cancer testis antigen NY-ESO-1 in melanoma patients.
Publication types: Journal Article ; Research Support
Cancer testis (CT) antigens are particularly interesting candidates for cancer vaccines. However, T-cell reactivity to CT antigens has been detected only occasionally in cancer patients, even after vaccination. A new group of CT antigens has been recently identified using the SEREX technique based on immunoscreening of tumor cDNA expression libraries with autologous sera. We have used fluorescent HLA-A2/peptide tetramers containing an optimized antigenic peptide to directly identify HLA-A2-restricted CD8+ T cells specific for the SEREX-defined CT antigen NY-ESO-1 in melanoma patients. High frequencies of NY-ESO-1-specific CD8+ T cells were readily detected in peptide-stimulated peripheral blood mononuclear cells as well as in lymphocytes infiltrating melanoma lesions from patients with measurable antibody responses to NY-ESO-1. NY-ESO-1-specific CD8+ T cells were also detectable in peptide-stimulated peripheral blood mononuclear cells from some seronegative patients. Whereas the frequencies of NY-ESO-1-specific CD8+ T cells in circulating lymphocytes were usually below the limit of detection by tetramer staining, the presence of NY-ESO-1 CD8+ T cells displaying a memory phenotype was clearly detectable ex vivo in blood from a seropositive patient over an extended period of time. These results indicate that sustained CD8+ T-cell responses to CT antigens can naturally occur both locally and systemically in melanoma patients.
Amino Acid Sequence, Antigens, Neoplasm/immunology, CD8-Positive T-Lymphocytes/immunology, Cancer Vaccines/immunology, Epitopes, T-Lymphocyte/immunology, HLA-A2 Antigen/immunology, Humans, Lymphocyte Activation/immunology, Lymphocytes, Tumor-Infiltrating/immunology, Male, Melanoma/blood, Melanoma/immunology, Membrane Proteins, Peptide Fragments/immunology, Proteins/immunology, T-Lymphocytes, Cytotoxic/immunology, Testis/immunology
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