title: Prognostic significance of HLA class I expression in osteosarcoma defined by anti-pan HLA class I monoclonal antibody, EMR8-5.
abstract: With the goal of establishing efficacious peptide-based immunotherapy for patients with bone and soft tissue sarcomas, we previously identified the cytotoxic T lymphocyte-defined osteosarcoma antigenic gene Papillomavirus binding factor. The present study was designed to determine the status of HLA class I expression in osteosarcoma and other bone and soft tissue sarcomas. Seventy-four formalin-fixed paraffin-embedded specimens of various bone and soft tissue sarcomas, including 33 osteosarcomas, were stained with the anti-HLA class I monoclonal antibody EMR8-5, which we recently generated. The expression of HLA class I was lost or downregulated in 46 of these specimens (62%). With respect to osteosarcoma, loss or downregulation of HLA class I expression was seen in 13 (52%) of 25 primary tumors and seven (88%) of eight metastatic tumors. In six of 11 HLA class I-negative osteosarcoma specimens, the expression of beta-2 microglobulin was also lost. Subsequently the prognostic significance of HLA class I expression was analyzed in 21 patients with osteosarcoma who had completed multidrug neoadjuvant chemotherapy and undergone adequate surgery. Patients with osteosarcoma highly expressing HLA class I showed significantly better overall and event-free survival than those with HLA class I-negative osteosarcoma. In contrast, such prognostic significance of HLA class I expression was not found in 15 patients with malignant fibrous histiocytoma of soft tissue. These findings suggest that the class I-restricted cytotoxic T lymphocyte pathway plays a major role in immune surveillance of patients with osteosarcoma.
authors.affiliation: Department of Orthopaedic Surgery, Sapporo Medical University School of Medicine, South 1, West 16, Chuo-ku, Sapporo 060-8543, Japan.
authors.forename: Tomohide
authors.initials: T
authors.lastname: Tsukahara
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kawaguchi
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Torigoe
authors.forename: Hiroko
authors.initials: H
authors.lastname: Asanuma
authors.forename: Emiri
authors.initials: E
authors.lastname: Nakazawa
authors.forename: Kumiko
authors.initials: K
authors.lastname: Shimozawa
authors.forename: Yuki
authors.initials: Y
authors.lastname: Nabeta
authors.forename: Shigeharu
authors.initials: S
authors.lastname: Kimura
authors.forename: Mitsunori
authors.initials: M
authors.lastname: Kaya
authors.forename: Satoshi
authors.initials: S
authors.lastname: Nagoya
authors.forename: Takuro
authors.initials: T
authors.lastname: Wada
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Yamashita
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Sato
mesh_terms: D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal / Q000276:immunology*; D001859:Bone Neoplasms / Q000276:immunology / Q000378:metabolism* / Q000556:secondary; D002648:Child; D005260:Female; D051677:Histiocytoma, Malignant Fibrous / Q000276:immunology / Q000473:pathology / Q000556:secondary; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D008297:Male; D008875:Middle Aged; D012516:Osteosarcoma / Q000175:diagnosis / Q000276:immunology / Q000378:metabolism*; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012509:Sarcoma / Q000276:immunology / Q000378:metabolism / Q000556:secondary; D012983:Soft Tissue Neoplasms / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015996:Survival Rate; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D001613:beta 2-Microglobulin / Q000235:genetics / Q000276:immunology / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D015395:Histocompatibility Antigens Class I; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D001613:beta 2-Microglobulin