Simard François A, Richert Iseulys, Vandermoeten Alexandra, Decouvelaere Anne-Valérie, Michot Jean-Philippe, Caux Christophe, Blay Jean-Yves, Dutour Aurélie
Cancer Research Center of Lyon, INSERM UMR 1052, CNRS UMR 5286, Centre Léon Berard , Lyon, France.
SCAR, Université Claude Bernard Lyon1, Faculté de médecine et de pharmacie de Rockefeller , Lyon, France.
Oncoimmunology. 2016 Dec 7;6(2):e1265716. doi: 10.1080/2162402X.2016.1265716. eCollection 2017.
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.
软骨肉瘤（CHS）是一种罕见的骨恶性肿瘤，其特征是对传统的全身治疗和放射治疗具有抗性。针对免疫检查点的免疫疗法在这些肿瘤中是否有效仍不清楚。为了探究免疫系统在这种肿瘤中的作用，我们分析了人类样本和同基因大鼠模型中软骨肉瘤的免疫环境，并测试了T淋巴细胞和巨噬细胞在软骨肉瘤进展中的作用。对人类软骨肉瘤样本和斯沃姆大鼠软骨肉瘤（SRC）模型进行了免疫组织化学染色。在SRC中进行了选择性免疫耗竭试验，以评估免疫细胞群对肿瘤进展的影响。在人类和大鼠软骨肉瘤中，在肿瘤周围区域发现了由淋巴细胞和巨噬细胞组成的免疫浸润。发现免疫浸润的组成与肿瘤特征和演变（分级、侵袭性和大小）相关。在SRC中，T淋巴细胞的选择性耗竭导致生长速度加快，而CD163巨噬细胞的耗竭则减缓了肿瘤进展。从携带CHS的SRC中分离出的脾细胞对软骨肉瘤细胞表现出特异性细胞毒性（27%），在CD3耗竭的SRC中这种细胞毒性显著降低（11%）。免疫环境在人类和动物模型中均有助于CHS的进展，这表明免疫调节方法可在骨软骨肉瘤中进行测试。
