Prognostic significance of HLA class I expression in osteosarcoma defined by anti-pan HLA class I monoclonal antibody, EMR8-5

Cancer Sci. 2006 Dec;97(12):1374-80. doi: 10.1111/j.1349-7006.2006.00317.x. Epub 2006 Sep 21.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antibodies, Monoclonal / immunology*
  • Bone Neoplasms / immunology
  • Bone Neoplasms / metabolism*
  • Bone Neoplasms / secondary
  • Child
  • Female
  • Histiocytoma, Malignant Fibrous / immunology
  • Histiocytoma, Malignant Fibrous / pathology
  • Histiocytoma, Malignant Fibrous / secondary
  • Histocompatibility Antigens Class I / genetics
  • Histocompatibility Antigens Class I / immunology
  • Histocompatibility Antigens Class I / metabolism*
  • Humans
  • Immunoenzyme Techniques
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Male
  • Middle Aged
  • Osteosarcoma / diagnosis
  • Osteosarcoma / immunology
  • Osteosarcoma / metabolism*
  • Prognosis
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA, Neoplasm / genetics
  • RNA, Neoplasm / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sarcoma / immunology
  • Sarcoma / metabolism
  • Sarcoma / secondary
  • Soft Tissue Neoplasms / immunology
  • Soft Tissue Neoplasms / metabolism
  • Soft Tissue Neoplasms / pathology
  • Survival Rate
  • T-Lymphocytes, Cytotoxic / immunology
  • beta 2-Microglobulin / genetics
  • beta 2-Microglobulin / immunology
  • beta 2-Microglobulin / metabolism


  • Antibodies, Monoclonal
  • Histocompatibility Antigens Class I
  • RNA, Messenger
  • RNA, Neoplasm
  • beta 2-Microglobulin