RT Journal Article SR Electronic T1 Naturally Occurring Human Lymphocyte Antigen-A2 Restricted CD8+ T-Cell Response to the Cancer Testis Antigen NY-ESO-1 in Melanoma Patients JF Cancer Research JO Cancer Res FD American Association for Cancer Research SP 4499 OP 4506 VO 60 IS 16 A1 Valmori, Danila A1 Dutoit, Valérie A1 Liénard, Danielle A1 Rimoldi, Donata A1 Pittet, Mikaël J. A1 Champagne, Patrick A1 Ellefsen, Kim A1 Sahin, Ugur A1 Speiser, Daniel A1 Lejeune, Ferdy A1 Cerottini, Jean-Charles A1 Romero, Pedro YR 2000 UL http://cancerres.aacrjournals.org/content/60/16/4499.abstract AB 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.