This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Valmori, D. Articles by Romero, P. Search for Related Content PubMed PubMed Citation Articles by Valmori, D. Articles by Romero, P.

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

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.

This article has been cited by other articles:

				L. Derre, M. Bruyninx, P. Baumgaertner, M. Ferber, D. Schmid, A. Leimgruber, V. Zoete, P. Romero, O. Michielin, D. E. Speiser, et al. Distinct sets of {alpha}{beta} TCRs confer similar recognition of tumor antigen NY-ESO-1157-165 by interacting with its central Met/Trp residues PNAS, September 30, 2008; 105(39): 15010 - 15015. [Abstract] [Full Text] [PDF]

				L. Derre, M. Bruyninx, P. Baumgaertner, E. Devevre, P. Corthesy, C. Touvrey, Y. D. Mahnke, H. Pircher, V. Voelter, P. Romero, et al. In Vivo Persistence of Codominant Human CD8+ T Cell Clonotypes Is Not Limited by Replicative Senescence or Functional Alteration J. Immunol., August 15, 2007; 179(4): 2368 - 2379. [Abstract] [Full Text] [PDF]

				M. Condomines, D. Hose, P. Raynaud, M. Hundemer, J. De Vos, M. Baudard, T. Moehler, V. Pantesco, M. Moos, J.-F. Schved, et al. Cancer/Testis Genes in Multiple Myeloma: Expression Patterns and Prognosis Value Determined by Microarray Analysis J. Immunol., March 1, 2007; 178(5): 3307 - 3315. [Abstract] [Full Text] [PDF]

				F. F. Costa, K. Le Blanc, and B. Brodin Concise Review: Cancer/Testis Antigens, Stem Cells, and Cancer Stem Cells, March 1, 2007; 25(3): 707 - 711. [Abstract] [Full Text] [PDF]

				S. M. Walton, M. Gerlinger, O. de la Rosa, N. Nuber, A. Knights, A. Gati, M. Laumer, L. Strauss, C. Exner, N. Schafer, et al. Spontaneous CD8 T Cell Responses against the Melanocyte Differentiation Antigen RAB38/NY-MEL-1 in Melanoma Patients J. Immunol., December 1, 2006; 177(11): 8212 - 8218. [Abstract] [Full Text] [PDF]

				G. Zeng, M. E. Aldridge, X. Tian, D. Seiler, X. Zhang, Y. Jin, J. Rao, W. Li, D. Chen, M. P. Langford, et al. Dendritic Cell Surface Calreticulin Is a Receptor for NY-ESO-1: Direct Interactions between Tumor-Associated Antigen and the Innate Immune System J. Immunol., September 15, 2006; 177(6): 3582 - 3589. [Abstract] [Full Text] [PDF]

				B. Janjic, P. Andrade, X.-F. Wang, J. Fourcade, C. Almunia, P. Kudela, A. Brufsky, S. Jacobs, D. Friedland, R. Stoller, et al. Spontaneous CD4+ T Cell Responses against TRAG-3 in Patients with Melanoma and Breast Cancers J. Immunol., August 15, 2006; 177(4): 2717 - 2727. [Abstract] [Full Text] [PDF]

				M. A. Purbhoo, D. H. Sutton, J. E. Brewer, R. E. Mullings, M. E. Hill, T. M. Mahon, J. Karbach, E. Jager, B. J. Cameron, N. Lissin, et al. Quantifying and Imaging NY-ESO-1/LAGE-1-Derived Epitopes on Tumor Cells Using High Affinity T Cell Receptors. J. Immunol., June 15, 2006; 176(12): 7308 - 7316. [Abstract] [Full Text] [PDF]

				P. Baumgaertner, N. Rufer, E. Devevre, L. Derre, D. Rimoldi, C. Geldhof, V. Voelter, D. Lienard, P. Romero, and D. E. Speiser Ex vivo Detectable Human CD8 T-Cell Responses to Cancer-Testis Antigens Cancer Res., February 15, 2006; 66(4): 1912 - 1916. [Abstract] [Full Text] [PDF]

				V. Vignard, B. Lemercier, A. Lim, M.-C. Pandolfino, Y. Guilloux, A. Khammari, C. Rabu, K. Echasserieau, F. Lang, M.-L. Gougeon, et al. Adoptive Transfer of Tumor-Reactive Melan-A-Specific CTL Clones in Melanoma Patients Is Followed by Increased Frequencies of Additional Melan-A-Specific T Cells J. Immunol., October 1, 2005; 175(7): 4797 - 4805. [Abstract] [Full Text] [PDF]

				M. Gannage, M. Abel, A.-S. Michallet, S. Delluc, M. Lambert, S. Giraudier, R. Kratzer, G. Niedermann, L. Saveanu, F. Guilhot, et al. Ex Vivo Characterization of Multiepitopic Tumor-Specific CD8 T Cells in Patients with Chronic Myeloid Leukemia: Implications for Vaccine Development and Adoptive Cellular Immunotherapy J. Immunol., June 15, 2005; 174(12): 8210 - 8218. [Abstract] [Full Text] [PDF]

				F. van Rhee, S. M. Szmania, F. Zhan, S. K. Gupta, M. Pomtree, P. Lin, R. B. Batchu, A. Moreno, G. Spagnoli, J. Shaughnessy, et al. NY-ESO-1 is highly expressed in poor-prognosis multiple myeloma and induces spontaneous humoral and cellular immune responses Blood, May 15, 2005; 105(10): 3939 - 3944. [Abstract] [Full Text] [PDF]

				N. Naka, S. Joyama, Y. Tsukamoto, K. Yoshioka, N. Hashimoto, T. Ujiiye, T. Hayashi, M. Kawase, M. Mano, S. Ishiguro, et al. Quantification of SSX mRNA Expression in Human Bone and Soft Tissue Tumors Using Nucleic Acid Sequence-Based Amplification J. Mol. Diagn., May 1, 2005; 7(2): 187 - 197. [Abstract] [Full Text] [PDF]

				M. Schnurr, Q. Chen, A. Shin, W. Chen, T. Toy, C. Jenderek, S. Green, L. Miloradovic, D. Drane, I. D. Davis, et al. Tumor antigen processing and presentation depend critically on dendritic cell type and the mode of antigen delivery Blood, March 15, 2005; 105(6): 2465 - 2472. [Abstract] [Full Text] [PDF]

				G. Bricard, H. Bouzourene, O. Martinet, D. Rimoldi, N. Halkic, M. Gillet, P. Chaubert, H. R. MacDonald, P. Romero, J.-C. Cerottini, et al. Naturally Acquired MAGE-A10- and SSX-2-Specific CD8+ T Cell Responses in Patients with Hepatocellular Carcinoma J. Immunol., February 1, 2005; 174(3): 1709 - 1716. [Abstract] [Full Text] [PDF]

				X.-Y. Shang, H.-S. Chen, H.-G. Zhang, X.-W. Pang, H. Qiao, J.-R. Peng, L.-L. Qin, R. Fei, M.-H. Mei, X.-S. Leng, et al. The Spontaneous CD8+ T-Cell Response to HLA-A2-Restricted NY-ESO-1b Peptide in Hepatocellular Carcinoma Patients Clin. Cancer Res., October 15, 2004; 10(20): 6946 - 6955. [Abstract] [Full Text] [PDF]

				M. Matsuo, Y. Nagata, E. Sato, D. Atanackovic, D. Valmori, Y.-T. Chen, G. Ritter, I. Mellman, L. J. Old, and S. Gnjatic IFN-{gamma} enables cross-presentation of exogenous protein antigen in human Langerhans cells by potentiating maturation PNAS, October 5, 2004; 101(40): 14467 - 14472. [Abstract] [Full Text] [PDF]

				C. Lonchay, P. van der Bruggen, T. Connerotte, T. Hanagiri, P. Coulie, D. Colau, S. Lucas, A. Van Pel, K. Thielemans, N. van Baren, et al. Correlation between tumor regression and T cell responses in melanoma patients vaccinated with a MAGE antigen PNAS, October 5, 2004; 101(suppl_2): 14631 - 14638. [Abstract] [Full Text] [PDF]

				M. van Oijen, A. Bins, S. Elias, J. Sein, P. Weder, G. de Gast, H. Mallo, M. Gallee, H. van Tinteren, T. Schumacher, et al. On the Role of Melanoma-Specific CD8+ T-Cell Immunity in Disease Progression of Advanced-Stage Melanoma Patients Clin. Cancer Res., July 15, 2004; 10(14): 4754 - 4760. [Abstract] [Full Text] [PDF]

				M. Ayyoub, C. S. Hesdorffer, G. Metthez, S. Stevanovic, G. Ritter, Y.-T. Chen, L. J. Old, D. Speiser, J.-C. Cerottini, and D. Valmori Identification of an SSX-2 Epitope Presented by Dendritic Cells to Circulating Autologous CD4+ T Cells J. Immunol., June 1, 2004; 172(11): 7206 - 7211. [Abstract] [Full Text] [PDF]

				A. I. Webb, M. A. Dunstone, W. Chen, M.-I. Aguilar, Q. Chen, H. Jackson, L. Chang, L. Kjer-Nielsen, T. Beddoe, J. McCluskey, et al. Functional and Structural Characteristics of NY-ESO-1-related HLA A2-restricted Epitopes and the Design of a Novel Immunogenic Analogue J. Biol. Chem., May 28, 2004; 279(22): 23438 - 23446. [Abstract] [Full Text] [PDF]

				E. Maraskovsky, S. Sjolander, D. P. Drane, M. Schnurr, T. T. T. Le, L. Mateo, T. Luft, K.-A. Masterman, T.-Y. Tai, Q. Chen, et al. NY-ESO-1 Protein Formulated in ISCOMATRIX Adjuvant Is a Potent Anticancer Vaccine Inducing Both Humoral and CD8+ T-Cell-Mediated Immunity and Protection against NY-ESO-1+ Tumors Clin. Cancer Res., April 15, 2004; 10(8): 2879 - 2890. [Abstract] [Full Text] [PDF]

				H. Gyobu, T. Tsuji, Y. Suzuki, T. Ohkuri, K. Chamoto, M. Kuroki, H. Miyoshi, Y. Kawarada, H. Katoh, T. Takeshima, et al. Generation and Targeting of Human Tumor-Specific Tc1 and Th1 Cells Transduced with a Lentivirus Containing a Chimeric Immunoglobulin T-Cell Receptor Cancer Res., February 15, 2004; 64(4): 1490 - 1495. [Abstract] [Full Text] [PDF]

				M. J. Palmowski, L. Lopes, Y. Ikeda, M. Salio, V. Cerundolo, and M. K. Collins Intravenous Injection of a Lentiviral Vector Encoding NY-ESO-1 Induces an Effective CTL Response J. Immunol., February 1, 2004; 172(3): 1582 - 1587. [Abstract] [Full Text] [PDF]

				M. Rodolfo, R. Luksch, E. Stockert, Y.-T. Chen, P. Collini, T. Ranzani, C. Lombardo, P. Dalerba, L. Rivoltini, F. Arienti, et al. Antigen-Specific Immunity in Neuroblastoma Patients: Antibody and T-Cell Recognition of NY-ESO-1 Tumor Antigen Cancer Res., October 15, 2003; 63(20): 6948 - 6955. [Abstract] [Full Text] [PDF]

				D. Nagorsen, C. Scheibenbogen, F. M. Marincola, A. Letsch, and U. Keilholz Natural T Cell Immunity against Cancer Clin. Cancer Res., October 1, 2003; 9(12): 4296 - 4303. [Abstract] [Full Text] [PDF]

				M. Ayyoub, D. Rimoldi, P. Guillaume, P. Romero, J.-C. Cerottini, D. Valmori, and D. Speiser Tumor-reactive, SSX-2-specific CD8+ T Cells Are Selectively Expanded during Immune Responses to Antigen-expressing Tumors in Melanoma Patients Cancer Res., September 1, 2003; 63(17): 5601 - 5606. [Abstract] [Full Text] [PDF]

				I. D. Davis, M. Jefford, P. Parente, and J. Cebon Rational approaches to human cancer immunotherapy J. Leukoc. Biol., January 1, 2003; 73(1): 3 - 29. [Abstract] [Full Text] [PDF]

				E.-F. Solomayer, M. Feuerer, L. Bai, V. Umansky, P. Beckhove, G. C. Meyberg, G. Bastert, V. Schirrmacher, and I. J. Diel Influence of Adjuvant Hormone Therapy and Chemotherapy on the Immune System Analysed in the Bone Marrow of Patients with Breast Cancer Clin. Cancer Res., January 1, 2003; 9(1): 174 - 180. [Abstract] [Full Text] [PDF]

				X. Zheng, J.-X. Gao, H. Zhang, T. L. Geiger, Y. Liu, and P. Zheng Clonal Deletion of Simian Virus 40 Large T Antigen-Specific T Cells in the Transgenic Adenocarcinoma of Mouse Prostate Mice: An Important Role for Clonal Deletion in Shaping the Repertoire of T Cells Specific for Antigens Overexpressed in Solid Tumors J. Immunol., November 1, 2002; 169(9): 4761 - 4769. [Abstract] [Full Text] [PDF]

				Y. Nagata, S. Ono, M. Matsuo, S. Gnjatic, D. Valmori, G. Ritter, W. Garrett, L. J. Old, and I. Mellman Differential presentation of a soluble exogenous tumor antigen, NY-ESO-1, by distinct human dendritic cell populations PNAS, August 6, 2002; 99(16): 10629 - 10634. [Abstract] [Full Text] [PDF]

				G. Zeng, Y. Li, M. El-Gamil, J. Sidney, A. Sette, R.-f. Wang, S. A. Rosenberg, and P. F. Robbins Generation of NY-ESO-1-specific CD4+ and CD8+ T Cells by a Single Peptide with Dual MHC Class I and Class II Specificities: A New Strategy for Vaccine Design Cancer Res., July 1, 2002; 62(13): 3630 - 3635. [Abstract] [Full Text] [PDF]

				D. Valmori, C. Scheibenbogen, V. Dutoit, D. Nagorsen, A. M. Asemissen, V. Rubio-Godoy, D. Rimoldi, P. Guillaume, P. Romero, D. Schadendorf, et al. Circulating Tumor-reactive CD8+ T Cells in Melanoma Patients Contain a CD45RA+CCR7- Effector Subset Exerting ex Vivo Tumor-specific Cytolytic Activity Cancer Res., March 1, 2002; 62(6): 1743 - 1750. [Abstract] [Full Text] [PDF]

				M. Ayyoub, S. Stevanovic, U. Sahin, P. Guillaume, C. Servis, D. Rimoldi, D. Valmori, P. Romero, J.-C. Cerottini, H.-G. Rammensee, et al. Proteasome-Assisted Identification of a SSX-2-Derived Epitope Recognized by Tumor-Reactive CTL Infiltrating Metastatic Melanoma J. Immunol., February 15, 2002; 168(4): 1717 - 1722. [Abstract] [Full Text] [PDF]

				V. Dutoit, V. Rubio-Godoy, M.-A. Doucey, P. Batard, D. Lienard, D. Rimoldi, D. Speiser, P. Guillaume, J.-C. Cerottini, P. Romero, et al. Functional Avidity of Tumor Antigen-Specific CTL Recognition Directly Correlates with the Stability of MHC/Peptide Multimer Binding to TCR J. Immunol., February 1, 2002; 168(3): 1167 - 1171. [Abstract] [Full Text] [PDF]

				V. Rubio-Godoy, V. Dutoit, D. Rimoldi, D. Lienard, F. Lejeune, D. Speiser, P. Guillaume, J.-C. Cerottini, P. Romero, and D. Valmori Discrepancy between ELISPOT IFN-gamma secretion and binding of A2/peptide multimers to TCR reveals interclonal dissociation of CTL effector function from TCR-peptide/MHC complexes half-life PNAS, August 17, 2001; (2001) 181348898. [Abstract] [Full Text] [PDF]

				V. Dutoit, V. Rubio-Godoy, P.-Y. Dietrich, A.-L. Quiqueres, V. Schnuriger, D. Rimoldi, D. Lienard, D. Speiser, P. Guillaume, P. Batard, et al. Heterogeneous T-Cell Response to MAGE-A10254-262: High Avidity-specific Cytolytic T Lymphocytes Show Superior Antitumor Activity Cancer Res., August 1, 2001; 61(15): 5850 - 5856. [Abstract] [Full Text] [PDF]

				T. Ono, T. Kurashige, N. Harada, Y. Noguchi, T. Saika, N. Niikawa, M. Aoe, S. Nakamura, T. Higashi, A. Hiraki, et al. Identification of proacrosin binding protein sp32 precursor as a human cancer/testis antigen PNAS, March 13, 2001; 98(6): 3282 - 3287. [Abstract] [Full Text] [PDF]

				P.-Y. Dietrich, P. R. Walker, A.-L. Quiquerez, G. Perrin, V. Dutoit, D. Liénard, P. Guillaume, J.-C. Cerottini, P. Romero, and D. Valmori Melanoma Patients Respond to a Cytotoxic T Lymphocyte-defined Self-Peptide with Diverse and Nonoverlapping T-Cell Receptor Repertoires Cancer Res., March 1, 2001; 61(5): 2047 - 2054. [Abstract] [Full Text]

				D. Valmori, V. Dutoit, V. Rubio-Godoy, C. Chambaz, D. Liénard, P. Guillaume, P. Romero, J.-C. Cerottini, and D. Rimoldi Frequent Cytolytic T-Cell Responses to Peptide MAGE-A10254-262 in Melanoma Cancer Res., January 1, 2001; 61(2): 509 - 512. [Abstract] [Full Text]

				D. Rimoldi, V. Rubio-Godoy, V. Dutoit, D. Lienard, S. Salvi, P. Guillaume, D. Speiser, E. Stockert, G. Spagnoli, C. Servis, et al. Efficient Simultaneous Presentation of NY-ESO-1/LAGE-1 Primary and Nonprimary Open Reading Frame-Derived CTL Epitopes in Melanoma J. Immunol., December 15, 2000; 165(12): 7253 - 7261. [Abstract] [Full Text] [PDF]

				V. Rubio-Godoy, V. Dutoit, D. Rimoldi, D. Lienard, F. Lejeune, D. Speiser, P. Guillaume, J.-C. Cerottini, P. Romero, and D. Valmori Discrepancy between ELISPOT IFN-gamma secretion and binding of A2/peptide multimers to TCR reveals interclonal dissociation of CTL effector function from TCR-peptide/MHC complexes half-life PNAS, August 28, 2001; 98(18): 10302 - 10307. [Abstract] [Full Text] [PDF]