HLA-restricted specific tumor cytolysis by autologous T-lymphocytes infiltrating metastatic bone malignant fibrous histiocytoma of lymph node
HLA-restricted specific tumor cytolysis by autologous T-lymphocytes infiltrating metastatic bone malignant fibrous histiocytoma of lymph node
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DOI：
10.1002/jor.20019
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发表时间：
2006-01-01
影响因子：
2.8
通讯作者：
Yamashita, TS
中科院分区：
文献类型：
--
作者：
Tsukahara, T;Kawaguchi, S;Yamashita, TS
骨恶性纤维组织细胞瘤(MFH)是一种高度恶性的肉瘤，组织学上以成纤维细胞和多形细胞组成为特征，具有明显的条纹状结构。尽管采取了多种治疗方法，但该肿瘤患者的预后仍不令人满意。在本研究中，为了开发主动免疫治疗的目标，我们从一位53岁的女性患者身上建立了四个细胞系，该女性患者患有肱骨MFH并有淋巴结转移。MFH2003和MFH2003-B7.1分别为原代病变来源细胞系及其B7.1转染体。B2003-EBV和TIL2003分别是从外周血淋巴细胞建立的B细胞系和从肿瘤侵袭的淋巴结建立的T细胞系。MFH2003细胞可在体外维持1年以上，并可移植到裸鼠体内。免疫组织化学分析细胞表型与原发肿瘤相似。TIL2003细胞均为CD8+，可特异性识别MFH2003细胞和MFH2003-B7.1细胞，但不能识别B2003-EBV细胞。抗HLAI类单抗完全阻断了TILs2003的抗MFH2003反应。这些发现表明在转移性淋巴结的微环境中存在抗MFH的特异性免疫反应。本研究建立的自体细胞系为筛选新的肿瘤相关抗原奠定了基础，并有望为骨MFH患者的免疫治疗奠定基础。(C)2005年骨科研究会。由威利期刊出版公司出版。
Malignant fibrous histiocytoma (MFH) of the bone is a high-grade sarcoma characterized histologically by the composition of fibroblasts and pleomorphic cells with a prominent storiform pattern. Despite institution of multi-modality treatments, the prognosis for patients with this tumor remains unsatisfactory. In the present study, towards the goal of developing active immunotherapy for those affected, we established four cell lines from a 53-year-old woman who suffered from MFH of the humerus with lymph node metastases. MFH2003 and MFH2003-B7.1 were the primary lesion-derived cell line and its B7.1-transfectant, respectively. B2003-EBV and TIL2003 were a B cell line established from peripheral blood lymphocytes and a T cell line established from tumor-invaded lymph nodes, respectively. MFH2003 cells could be maintained over a period of I year in vitro, and could be xenotransplanted into nude mice. The phenotype of cells analyzed by immunostaining was similar to the original tumor. TIL2003 cells were all CD8+ and specifically recognized MFH2003 cells and MFH2003-B7.1 cells, but not B2003-EBV cells. An anti-HLA-class I monoclonal antibody completely blocked the anti-MFH2003 response of TILs2003. These findings indicate the existence of an anti-MFH specific immune response in the microenvironment of metastatic lymph nodes. The present autologous cell lines provide the basis for identification of novel tumor-associated antigens and may be helpful in the establishment of immunotherapy for patients with MFH of the bone. (c) 2005 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.