title: Dendritic and mast cell involvement in the inflammatory response to primary malignant bone tumours.
abstract: BACKGROUND
  A chronic inflammatory cell infiltrate is commonly seen in response to primary malignant tumours of bone. This is known to contain tumour-associated macrophages (TAMs) and lymphocytes; dendritic cells (DCs) and mast cells (MCs) have also been identified but whether these and other inflammatory cells are seen commonly in specific types of bone sarcoma is uncertain.
  
  
  METHODS
  In this study we determined the nature of the inflammatory cell infiltrate in 56 primary bone sarcomas. Immunohistochemistry using monoclonal antibodies was employed to assess semiquantitatively CD45+ leukocyte infiltration and the extent of the DC, MC, TAM and T and B lymphocyte infiltrate.
  
  
  RESULTS
  The extent of the inflammatory infiltrate in individual sarcomas was very variable. A moderate or heavy leukocyte infiltrate was more commonly seen in conventional high-grade osteosarcoma, undifferentiated pleomorphic sarcoma and giant cell tumour of bone (GCTB) than in Ewing sarcoma, chordoma and chondrosarcoma. CD14+/CD68+ TAMs and CD3+ T lymphocytes were the major components of the inflammatory cell response but (DC-SIGN/CD11c+) DCs were also commonly noted when there was a significant TAM and T lymphocyte infiltrate. MCs were identified mainly at the periphery of sarcomas, including the osteolytic tumour-bone interface.
  
  
  CONCLUSIONS
  Our findings indicate that, although variable, some malignant bone tumours (e.g. osteosarcoma, GCTB) are more commonly associated with a pronounced inflammatory cell infiltrate than others (e.g. chondrosarcoma. Ewing sarcoma); the infiltrate is composed mainly of TAMs but includes a significant DC, T lymphocyte and MC infiltrate.
  
  
  CONCLUSIONS
  Tumours that contain a heavy inflammatory cell response, which includes DCs, TAMs and T lymphocytes, may be more amenable to immunomodulatory therapy. MCs are present mainly at the tumour edge and are likely to contribute to osteolysis and tumour invasion.
authors.affiliation: Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal and Sciences, University of Oxford, Nuffield Orthopaedic Centre, Oxford, OX3 7HE UK ; Department of Orthopaedic Surgery, Nara Medical University, Kashihara, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Inagaki
authors.affiliation: Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal and Sciences, University of Oxford, Nuffield Orthopaedic Centre, Oxford, OX3 7HE UK.
authors.forename: E
authors.initials: E
authors.lastname: Hookway
authors.affiliation: Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal and Sciences, University of Oxford, Nuffield Orthopaedic Centre, Oxford, OX3 7HE UK.
authors.forename: K A
authors.initials: KA
authors.lastname: Williams
authors.affiliation: Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal and Sciences, University of Oxford, Nuffield Orthopaedic Centre, Oxford, OX3 7HE UK.
authors.forename: A B
authors.initials: AB
authors.lastname: Hassan
authors.affiliation: Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal and Sciences, University of Oxford, Nuffield Orthopaedic Centre, Oxford, OX3 7HE UK.
authors.forename: U
authors.initials: U
authors.lastname: Oppermann
authors.affiliation: Department of Orthopaedic Surgery, Nara Medical University, Kashihara, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Tanaka
authors.affiliation: Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal and Sciences, University of Oxford, Nuffield Orthopaedic Centre, Oxford, OX3 7HE UK.
authors.forename: E
authors.initials: E
authors.lastname: Soilleux
authors.affiliation: Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal and Sciences, University of Oxford, Nuffield Orthopaedic Centre, Oxford, OX3 7HE UK.
authors.forename: N A
authors.initials: NA
authors.lastname: Athanasou
keywords: Bone sarcomas; Dendritic cells; Immunity; Lymphocytes; Macrophages; Mast cells