title: Naturally acquired MAGE-A10- and SSX-2-specific CD8+ T cell responses in patients with hepatocellular carcinoma.
abstract: 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.
authors.affiliation: Division of Clinical Onco-Immunology, Ludwig Institute for Cancer Research, Lausanne, Switzerland.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Bricard
authors.forename: Hanifa
authors.initials: H
authors.lastname: Bouzourene
authors.forename: Olivier
authors.initials: O
authors.lastname: Martinet
authors.forename: Donata
authors.initials: D
authors.lastname: Rimoldi
authors.forename: Nermin
authors.initials: N
authors.lastname: Halkic
authors.forename: Michel
authors.initials: M
authors.lastname: Gillet
authors.forename: Pascal
authors.initials: P
authors.lastname: Chaubert
authors.forename: H Robson
authors.initials: HR
authors.lastname: Macdonald
authors.forename: Pedro
authors.initials: P
authors.lastname: Romero
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Cerottini
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Speiser
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D017951:Antigen Presentation; D000951:Antigens, Neoplasm / Q000096:biosynthesis / Q000276:immunology; D000954:Antigens, Surface; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D006528:Carcinoma, Hepatocellular / Q000276:immunology* / Q000473:pathology; D045744:Cell Line, Tumor; D003601:Cytotoxicity Tests, Immunologic; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D015789:HLA-A2 Antigen / Q000096:biosynthesis; D006801:Humans; D007113:Immunity, Innate; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000276:immunology* / Q000473:pathology; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D008545:Melanoma / Q000276:immunology; D008565:Membrane Proteins / Q000096:biosynthesis / Q000276:immunology; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000276:immunology*; D012097:Repressor Proteins / Q000096:biosynthesis / Q000276:immunology*
chemical_list: D000951:Antigens, Neoplasm; D000954:Antigens, Surface; C104948:CTAG1B protein, human; C510162:CTAG2 protein, human; D018984:Epitopes, T-Lymphocyte; D015789:HLA-A2 Antigen; C119317:MAGE-A10 antigen; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D012097:Repressor Proteins; C093962:synovial sarcoma X breakpoint proteins