Prognostic significance of HLA class I expression in osteosarcoma defined by anti-pan HLA class I monoclonal antibody, EMR8-5
| Autor: | Shigeharu Kimura, Yuki Nabeta, Satoshi Kawaguchi, Kumiko Shimozawa, Satoshi Nagoya, Takuro Wada, Toshihiko Torigoe, Noriyuki Sato, Toshihiko Yamashita, Emiri Nakazawa, Tomohide Tsukahara, Mitsunori Kaya, Hiroko Asanuma |
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| Rok vydání: | 2006 |
| Předmět: |
Adult
Male musculoskeletal diseases Cancer Research Pathology medicine.medical_specialty Adolescent medicine.medical_treatment Bone Neoplasms Soft Tissue Neoplasms Histiocytoma Malignant Fibrous Human leukocyte antigen Immunoenzyme Techniques Lymphocytes Tumor-Infiltrating Antigen Humans Medicine Cytotoxic T cell RNA Messenger RNA Neoplasm Child Osteosarcoma biology Reverse Transcriptase Polymerase Chain Reaction business.industry Beta-2 microglobulin Histocompatibility Antigens Class I Antibodies Monoclonal Sarcoma General Medicine Immunotherapy Middle Aged Prognosis medicine.disease Survival Rate Oncology biology.protein Cancer research Female Antibody beta 2-Microglobulin business T-Lymphocytes Cytotoxic |
| Zdroj: | Cancer Science. 97:1374-1380 |
| ISSN: | 1349-7006 1347-9032 |
| DOI: | 10.1111/j.1349-7006.2006.00317.x |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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