title: Cancer-testis antigen 7 expression and immune responses following allogeneic stem cell transplantation for multiple myeloma.
abstract: Cancer-testis antigen 7 (CT7) is the most frequently and consistently expressed MAGE antigen in multiple myeloma, exhibits tissue-restricted expression, and is an independent negative prognostic factor for multiple myeloma. We sought to characterize CT7 protein expression in the bone marrow of patients with multiple myeloma undergoing allogeneic T cell-depleted hematopoietic stem cell transplantation (alloTCD-HSCT), and to examine the significance of CT7-specific cellular immune responses. We further aimed to determine CT7-derived immunogenic epitopes and their associated allelic restrictions. CT7 protein expression in neoplastic CD138(+) plasma cells was evaluated by immunohistochemistry in bone marrow biopsies from 10 patients. CT7 was present in 8 of 10 patients. Longitudinal analyses of the 10 patients revealed an association between CT7 expression and prognosis. Longitudinal monitoring of CT7-specific T cells revealed an association between increased frequencies of CT7-specific T cells and reductions in specific myeloma markers. Epitope-specific reactivity to the nonamer FLAMLKNTV was detected by intracellular IFNγ assay in peripheral blood (PB) and bone marrow-derived T cells from HLA-A*0201(+) patients. Serial monitoring of PB CT7-specific T-cell frequencies in 4 HLA-A*0201(+) patients by HLA-A*0201-CT7(1087-1095) tetramer staining revealed an association with disease course. Phenotypic analyses revealed bone marrow enrichment for central memory CT7-specific T cells, while effector memory cells dominated the PB. Together, these findings support the development of immunotherapeutic strategies that aim to enhance CT7-directed immune responses for the treatment of multiple myeloma.
authors.affiliation: Authors' Affiliations: Immunology and Microbial Pathogenesis Program, Weill Cornell Graduate School of Medical Sciences; Sloan-Kettering Institute; Department of Pathology, Bone Marrow Transplant Service, Department of Pediatrics, and Adult Bone Marrow Transplant Service, Division of Hematologic Oncology, Department of Medicine, Memorial Sloan-Kettering Cancer Center; The Tisch Cancer Institute, Hess Center for Science and Medicine, Icahn School of Medicine at Mount Sinai; and Weill Medical College of Cornell University, New York, New YorkAuthors' Affiliations: Immunology and Microbial Pathogenesis Program, Weill Cornell Graduate School of Medical Sciences; Sloan-Kettering Institute; Department of Pathology, Bone Marrow Transplant Service, Department of Pediatrics, and Adult Bone Marrow Transplant Service, Division of Hematologic Oncology, Department of Medicine, Memorial Sloan-Kettering Cancer Center; The Tisch Cancer Institute, Hess Center for Science and Medicine, Icahn School of Medicine at Mount Sinai; and Weill Medical College of Cornell University, New York, New York.
authors.forename: Eleanor M
authors.initials: EM
authors.lastname: Tyler
authors.affiliation: Authors' Affiliations: Immunology and Microbial Pathogenesis Program, Weill Cornell Graduate School of Medical Sciences; Sloan-Kettering Institute; Department of Pathology, Bone Marrow Transplant Service, Department of Pediatrics, and Adult Bone Marrow Transplant Service, Division of Hematologic Oncology, Department of Medicine, Memorial Sloan-Kettering Cancer Center; The Tisch Cancer Institute, Hess Center for Science and Medicine, Icahn School of Medicine at Mount Sinai; and Weill Medical College of Cornell University, New York, New York.
authors.forename: Achim A
authors.initials: AA
authors.lastname: Jungbluth
authors.affiliation: Authors' Affiliations: Immunology and Microbial Pathogenesis Program, Weill Cornell Graduate School of Medical Sciences; Sloan-Kettering Institute; Department of Pathology, Bone Marrow Transplant Service, Department of Pediatrics, and Adult Bone Marrow Transplant Service, Division of Hematologic Oncology, Department of Medicine, Memorial Sloan-Kettering Cancer Center; The Tisch Cancer Institute, Hess Center for Science and Medicine, Icahn School of Medicine at Mount Sinai; and Weill Medical College of Cornell University, New York, New York.
authors.forename: Sacha
authors.initials: S
authors.lastname: Gnjatic
authors.affiliation: Authors' Affiliations: Immunology and Microbial Pathogenesis Program, Weill Cornell Graduate School of Medical Sciences; Sloan-Kettering Institute; Department of Pathology, Bone Marrow Transplant Service, Department of Pediatrics, and Adult Bone Marrow Transplant Service, Division of Hematologic Oncology, Department of Medicine, Memorial Sloan-Kettering Cancer Center; The Tisch Cancer Institute, Hess Center for Science and Medicine, Icahn School of Medicine at Mount Sinai; and Weill Medical College of Cornell University, New York, New YorkAuthors' Affiliations: Immunology and Microbial Pathogenesis Program, Weill Cornell Graduate School of Medical Sciences; Sloan-Kettering Institute; Department of Pathology, Bone Marrow Transplant Service, Department of Pediatrics, and Adult Bone Marrow Transplant Service, Division of Hematologic Oncology, Department of Medicine, Memorial Sloan-Kettering Cancer Center; The Tisch Cancer Institute, Hess Center for Science and Medicine, Icahn School of Medicine at Mount Sinai; and Weill Medical College of Cornell University, New York, New YorkAuthors' Affiliations: Immunology and Microbial Pathogenesis Program, Weill Cornell Graduate School of Medical Sciences; Sloan-Kettering Institute; Department of Pathology, Bone Marrow Transplant Service, Department of Pediatrics, and Adult Bone Marrow Transplant Service, Division of Hematologic Oncology, Department of Medicine, Memorial Sloan-Kettering Cancer Center; The Tisch Cancer Institute, Hess Center for Science and Medicine, Icahn School of Medicine at Mount Sinai; and Weill Medical College of Cornell University, New York, New York.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: O'Reilly
authors.affiliation: Authors' Affiliations: Immunology and Microbial Pathogenesis Program, Weill Cornell Graduate School of Medical Sciences; Sloan-Kettering Institute; Department of Pathology, Bone Marrow Transplant Service, Department of Pediatrics, and Adult Bone Marrow Transplant Service, Division of Hematologic Oncology, Department of Medicine, Memorial Sloan-Kettering Cancer Center; The Tisch Cancer Institute, Hess Center for Science and Medicine, Icahn School of Medicine at Mount Sinai; and Weill Medical College of Cornell University, New York, New YorkAuthors' Affiliations: Immunology and Microbial Pathogenesis Program, Weill Cornell Graduate School of Medical Sciences; Sloan-Kettering Institute; Department of Pathology, Bone Marrow Transplant Service, Department of Pediatrics, and Adult Bone Marrow Transplant Service, Division of Hematologic Oncology, Department of Medicine, Memorial Sloan-Kettering Cancer Center; The Tisch Cancer Institute, Hess Center for Science and Medicine, Icahn School of Medicine at Mount Sinai; and Weill Medical College of Cornell University, New York, New York koehneg@mskcc.org.
authors.forename: Guenther
authors.initials: G
authors.lastname: Koehne
mesh_terms: D000951:Antigens, Neoplasm / Q000378:metabolism*; D001853:Bone Marrow / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D018450:Disease Progression; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D015789:HLA-A2 Antigen / Q000378:metabolism; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology*; D009101:Multiple Myeloma / Q000276:immunology* / Q000628:therapy; D014184:Transplantation, Homologous
chemical_list: D000951:Antigens, Neoplasm; C473332:CT7 antigen, human; D018984:Epitopes, T-Lymphocyte; D015789:HLA-A2 Antigen