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 formalinfixed 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 β β 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)

A phase I study of vaccination with NY‐ESO‐1f peptide mixed with Picibanil OK‐432 and Montanide ISA‐51 in patients with cancers expressing the NY‐ESO‐1 antigen

“…3 E978 23 and EMR8-5 (Funakoshi, Tokyo, Japan) 24 mAbs were used to analyze NY-ESO-1 and HLA class I expression, respectively. The reaction was evaluated as þþþ (>50% stained cells), þþ (25-50% stained cells), þ (5-25% stained cells) and À (<5% stained cells).…”

Targets for active immunotherapy against pediatric solid tumors

“…Tumor-inWltrating immune cells have frequently been observed in a wide variety of pediatric tumors [103,125]. Tumor inWltration of lymphocytes is generally associated with a more favorable prognosis and occasionally tumor regression [34,119].…”

Cancer immunotherapy: a brief review of the history, possibilities, and challenges ahead

“…In the escape phase, cancer cells grow and metastasize due to loss of control by the immune system. The cancer cells which are not eliminated and which escape may do this by expressing fewer antigens on their surfaces or even by losing their MHC class I expression [34] . They may also show the ability to protect themselves from T-cell attack by expressing immune checkpoint (IC) molecules on their surfaces like normal cells; these IC molecules are upregulated by cytokines produced by activated T-cells and are part of a normal negative feedback loop to control excessive tissue damage from inflammation by downregulating or suppressing T-cells [35] .…”