title: Description of the immune microenvironment of chondrosarcoma and contribution to progression.
abstract: Chondrosarcoma (CHS) is a rare bone malignancy characterized by its resistance to conventional systemic and radiation therapies. Whether immunotherapy targeting immune checkpoints may be active in these tumors remains unknown. To explore the role of the immune system in this tumor, we analyzed the immune environment of chondrosarcomas both in human sample, and in a syngeneic rat model, and tested the contribution of T lymphocytes and macrophages in chondrosarcoma progression. Immunohistochemical stainings were performed on human chondrosarcoma samples and on Swarm rat chondrosarcoma (SRC) model. Selective immunodepletion assays were performed in SRC to evaluate immune population's involvement in tumor progression. In human and rat chondrosarcoma, immune infiltrates composed of lymphocytes and macrophages were identified in the peritumoral area. Immune infiltrates composition was found correlated with tumors characteristics and evolution (grade, invasiveness and size). In SRC, selective depletion of T lymphocytes resulted in an accelerated growth rates, whereas depletion of CD163+macrophages slowed down tumor progression. Splenocytes isolated from CHS-bearing SRC showed a specific cytotoxicity directed against chondrosarcoma cells (27%), which significantly decreased in CD3-depleted SRC (11%). The immune environment contributes to CHS progression in both human and animal models, suggesting that immunomodulatory approaches could be tested in bone chondrosarcoma.
authors.affiliation: Cancer Research Center of Lyon, INSERM UMR 1052, CNRS UMR 5286, Centre Léon Berard , Lyon, France.
authors.forename: François A
authors.initials: FA
authors.lastname: Simard
authors.affiliation: Cancer Research Center of Lyon, INSERM UMR 1052, CNRS UMR 5286, Centre Léon Berard , Lyon, France.
authors.forename: Iseulys
authors.initials: I
authors.lastname: Richert
authors.affiliation: SCAR, Université Claude Bernard Lyon1, Faculté de médecine et de pharmacie de Rockefeller , Lyon, France.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Vandermoeten
authors.affiliation: Pathology Department, Centre Leon Berard , Lyon, France.
authors.forename: Anne-Valérie
authors.initials: AV
authors.lastname: Decouvelaere
authors.affiliation: Pathology Department, Centre Leon Berard , Lyon, France.
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Michot
authors.affiliation: Cancer Research Center of Lyon, INSERM UMR 1052, CNRS UMR 5286, Centre Léon Berard , Lyon, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Caux
authors.affiliation: Medical Oncology Department, Centre Leon Berard , Lyon, France.
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Blay
authors.affiliation: Cancer Research Center of Lyon, INSERM UMR 1052, CNRS UMR 5286, Centre Léon Berard , Lyon, France.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Dutour
keywords: Chondrosarcoma; T lymphocytes; immune infiltrates; immunotherapy; macrophages