Open AccessPrognostic significance of HLA class I expression in osteosarcoma defined by anti‐pan HLA class I monoclonal antibody, EMR8‐5
Author(s) -
Tsukahara Tomohide,
Kawaguchi Satoshi,
Torigoe Toshihiko,
Asanuma Hiroko,
Nakazawa Emiri,
Shimozawa Kumiko,
Nabeta Yuki,
Kimura Shigeharu,
Kaya Mitsunori,
Nagoya Satoshi,
Wada Takuro,
Yamashita Toshihiko,
Sato Noriyuki
Publication year - 2006
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2006.00317.x
Subject(s) - osteosarcoma , human leukocyte antigen , sarcoma , monoclonal antibody , medicine , cancer research , immunohistochemistry , cytotoxic t cell , immunotherapy , pathology , immunology , antibody , immune system , biology , antigen , in vitro , biochemistry
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 β‐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. ( Cancer Sci 2006; 97: 1374–1380)