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[Cancer Research 60, 4499-4506, August 15, 2000]
© 2000 American Association for Cancer Research

Immunology

Naturally Occurring Human Lymphocyte Antigen-A2 Restricted CD8+ T-Cell Response to the Cancer Testis Antigen NY-ESO-1 in Melanoma Patients1

Danila Valmori2, Valérie Dutoit, Danielle Liénard, Donata Rimoldi, Mikaël J. Pittet, Patrick Champagne, Kim Ellefsen, Ugur Sahin, Daniel Speiser, Ferdy Lejeune, Jean-Charles Cerottini and Pedro Romero

Division of Clinical Onco-Immunology, Ludwig Institute for Cancer Research, Lausanne Branch [D. V., V. D., D. L., D. R., M. J. P., D. S., J-C. C., P. R.], and Multidisciplinary Oncology Center [D. L., F. L.], University Hospital, 1011 Lausanne, Switzerland; Laboratoire d’Immunologie, Institut de Recherches Cliniques de Montréal, HZW IR7 Québec, Canada [P. C., K. E.]; Department of Medicine, Division of Experimental Medicine, McGill University, Montréal, Québec H3A 1A3, Canada [P. C.]; and Department of Internal Medicine I, Saarland University Medical School, D-66421 Homburg, Germany [U. S.]

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.




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