HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

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

Naturally Acquired MAGE-A10- and SSX-2-Specific CD8⁺ T Cell Responses in Patients with Hepatocellular Carcinoma¹

Gabriel Bricard^*, Hanifa Bouzourene, Olivier Martinet^2,, Donata Rimoldi, Nermin Halkic, Michel Gillet, Pascal Chaubert, H. Robson MacDonald, Pedro Romero^*, Jean-Charles Cerottini^*, and Daniel E. Speiser^3,*

^* Division of Clinical Onco-Immunology, Ludwig Institute for Cancer Research, Institut Universitaire de Pathologie, and Department of Surgery, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland; and Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, Epalinges, Switzerland

Immunotherapy is being proposed to treat patients with hepatocellular carcinoma (HCC). However, more detailed knowledge on tumor Ag expression and specific immune cells is required for the preparation of highly targeted vaccines. HCC express a variety of tumor-specific Ags, raising the question whether CTL specific for such Ags exist in HCC patients. Indeed, a recent study revealed CTLs specific for two cancer-testis (CT) Ags (MAGE-A1 and MAGE-A3) in tumor infiltrating lymphocytes of HCC patients. Here we assessed the presence of T cells specific for additional CT Ags: MAGE-A10, SSX-2, NY-ESO-1, and LAGE-1, which are naturally immunogenic as demonstrated in HLA-A2⁺ melanoma patients. In two of six HLA-A2⁺ HCC patients, we found that MAGE-A10- and/or SSX-2-specific CD8⁺ T cells naturally responded to the disease, because they were enriched in tumor lesions but not in nontumoral liver. Isolated T cells specifically and strongly killed tumor cells in vitro, providing evidence that these CTL were selected in vivo for high avidity Ag recognition. Therefore, besides melanoma, HCC is the second solid human tumor with clear evidence for in vivo tumor recognition by T cells, providing the rational for specific immunotherapy, based on immunization with CT Ags such as MAGE-A10 and SSX-2.

This article has been cited by other articles:

				G. Bricard, V. Cesson, E. Devevre, H. Bouzourene, C. Barbey, N. Rufer, J. S. Im, P. M. Alves, O. Martinet, N. Halkic, et al. Enrichment of Human CD4+ V{alpha}24/V{beta}11 Invariant NKT Cells in Intrahepatic Malignant Tumors J. Immunol., April 15, 2009; 182(8): 5140 - 5151. [Abstract] [Full Text] [PDF]

				Q. Gao, X.-Y. Wang, S.-J. Qiu, I. Yamato, M. Sho, Y. Nakajima, J. Zhou, B.-Z. Li, Y.-H. Shi, Y.-S. Xiao, et al. Overexpression of PD-L1 Significantly Associates with Tumor Aggressiveness and Postoperative Recurrence in Human Hepatocellular Carcinoma Clin. Cancer Res., February 1, 2009; 15(3): 971 - 979. [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]