Naturally Occurring Human Lymphocyte Antigen-A2 Restricted CD8+ T-Cell Response to the Cancer Testis Antigen NY-ESO-1 in Melanoma Patients

D Valmori, V Dutoit, D Liénard, D Rimoldi, MJ Pittet… - Cancer research, 2000 - AACR
D Valmori, V Dutoit, D Liénard, D Rimoldi, MJ Pittet, P Champagne, K Ellefsen, U Sahin
Cancer research, 2000AACR
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 …
Abstract
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.
AACR