title: Expression of the immune regulation antigen CD70 in osteosarcoma.
abstract: Osteosarcoma is the most frequent bone cancer in children and young adults. The outcome of patients with advanced disease is dismal. Exploitation of tumor-immune cell interactions may provide novel therapeutic approaches. CD70-CD27 interactions are important for the regulation of adaptive immunity. CD70 expression has been reported in some solid cancers and implicated in tumor escape from immunosurveillance. In this study, expression of CD70 and CD27 was analyzed in osteosarcoma cell lines and tumor specimens. CD70 protein was expressed on most osteosarcoma cell lines (5/7) and patient-derived primary osteosarcoma cultures (4/6) as measured by flow cytometry. In contrast, CD70 was detected on few Ewing sarcoma cell lines (5/15) and was virtually absent from neuroblastoma (1/7) and rhabdomyosarcoma cell lines (0/5). CD70(+) primary cultures were derived from CD70(+) osteosarcoma lesions. CD70 expression in osteosarcoma cryosections was heterogeneous, restricted to tumor cells and not attributed to infiltrating CD3(+) T cells as assessed by immunohistochemistry/immunofluorescence. CD70 was detected in primary (1/5) but also recurrent (2/4) and metastatic (1/3) tumors. CD27, the receptor for CD70, was neither detected on tumor cells nor on T cells in CD70(+) or CD70(-) tumors, suggesting that CD70 on tumor cells is not involved in CD27-dependent tumor-immune cell interactions in osteosarcoma. CD70 gene expression in diagnostic biopsies of osteosarcoma patients did not correlate with the occurrence of metastasis and survival (n = 70). Our data illustrate that CD70 is expressed in a subset of osteosarcoma patients. In patients with CD70(+) tumors, CD70 may represent a novel candidate for antibody-based targeted immunotherapy.
authors: Department of Pediatrics, Leiden University Medical Center, 2333ZA Leiden, The Netherlands ; Innate Immunity Group, German Cancer Research Center, 69120 Heidelberg, Germany.
authors: Jens Hw
authors: JH
authors: Pahl
authors: Department of Pediatrics, Leiden University Medical Center, 2333ZA Leiden, The Netherlands.
authors: Susy J
authors: SJ
authors: Santos
authors: Department of Pathology, Leiden University Medical Center, 2333ZA Leiden, The Netherlands.
authors: Marieke L
authors: ML
authors: Kuijjer
authors: Department of Pediatrics, Leiden University Medical Center, 2333ZA Leiden, The Netherlands.
authors: Gerharda H
authors: GH
authors: Boerman
authors: Department of Pathology, Leiden University Medical Center, 2333ZA Leiden, The Netherlands.
authors: Laurens Gl
authors: LG
authors: Sand
authors: Department of Molecular Cell Biology, Leiden University Medical Center, 2333ZA Leiden, The Netherlands.
authors: Karoly
authors: K
authors: Szuhai
authors: Department of Pathology, Leiden University Medical Center, 2333ZA Leiden, The Netherlands.
authors: Annemarie
authors: A
authors: Cleton-Jansen
authors: Division of Hematology/Oncology, Hospital for Sick Children/University of Toronto, M5G1X8 Toronto, Canada.
authors: R Maarten
authors: RM
authors: Egeler
authors: Department of Pathology, Leiden University Medical Center, 2333ZA Leiden, The Netherlands.
authors: Judith Vmg
authors: JV
authors: Boveé
authors: Department of Pediatrics, Leiden University Medical Center, 2333ZA Leiden, The Netherlands.
authors: Marco W
authors: MW
authors: Schilham
authors: Department of Pediatrics, Leiden University Medical Center, 2333ZA Leiden, The Netherlands.
authors: Arjan C
authors: AC
authors: Lankester
keywords: CD27; CD70; Immunotherapy; Osteosarcoma