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.
Highlights
Osteosarcoma is the most frequent bone cancer in children and adolescents
We demonstrate that CD70 is expressed on the majority of osteosarcoma cell lines as well as patient-derived osteosarcoma cultures which were derived from CD70+ tumor tissue
CD70 gene expression in diagnostic biopsies was significantly higher in a subset of osteosarcoma patients but this difference was not correlated with metastasis-free survival
Summary
Osteosarcoma is the most frequent bone cancer in children and adolescents. Despite intensive chemotherapy, patients with recurrent, metastatic and chemotherapyrefractory osteosarcoma have a poor prognosis [1]. Osteosarcoma is frequently infiltrated by immune cells such as macrophages and T cells [2,3]. CD70 is the natural ligand for the tumor necrosis factor (TNF) superfamily member CD27 and has originally been described as a co-stimulatory molecule for B cell and T cell activation [4,5]. CD70 is absent from human and murine naïve T cells, immature B cells and Natural Killer (NK) cells, but induced by T cell and B cell receptor triggering, B cell transformation or NK cell activation by interleukin-15 (IL-15) [4,8]. While absent from immature dendritic cells and neutrophils [9], CD70 expression can be induced on myeloid and plasmacytoid dendritic cells by e.g. toll-like receptor ligands in combination with CD40 ligation [10,11]. Interaction of CD70 with its receptor CD27 has originally been demonstrated to enhance the expansion, interferon-γ (IFN-γ) and IL-2
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