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从两名长期存活的肺癌患者中获得肿瘤特异性细胞溶解T细胞克隆。

Derivation of tumor-specific cytolytic T-cell clones from two lung cancer patients with long survival.

作者信息

Weynants P, Thonnard J, Marchand M, Delos M, Boon T, Coulie P G

机构信息

Ludwig Institute for Cancer Research, Brussels, Services de Pneumologie et d'Anatomopathologie, Hôpital de Mont-Godinne, Université Catholique de Louvain, Yvoir; and Cellular Genetics Unit, Université Catholique de Louvain, Brussels,Belgium.

出版信息

Am J Respir Crit Care Med. 1999 Jan;159(1):55-62. doi: 10.1164/ajrccm.159.1.9805073.

DOI:10.1164/ajrccm.159.1.9805073
PMID:9872818
Abstract

We derived lung carcinoma cell lines from tumor material resected from a patient with small-cell lung cancer (SCLC) and from a patient with non-small-cell lung cancer (NSCLC). The patient with NSCLC was vaccinated with irradiated autologous tumor cells. The two patients enjoyed an exceptionally favorable clinical evolution and are currently without signs of cancer 10 and 8 yr after their diagnoses, respectively. Autologous mixed lymphocyte-tumor cell cultures (MLTC) were produced with blood lymphocytes stimulated with irradiated autologous tumor cells. The first patient's SCLC cells, which carried a small amount of human leukocyte antigen (HLA) class I molecules, were incubated with interferon-gamma (IFN-gamma) before being used as stimulator cells. A cytolytic T-lymphocyte (CTL) clone was derived that specifically lysed the IFN-gamma-treated SCLC cells but did not lyse untreated tumor cells or autologous lymphoblasts. Clones of autologous tumor-specific CTL, directed against the NSCLC cells of the other patient, were also obtained. These tumor cells carried a higher level of HLA class I molecules and were lysed by the CTL without incubation with IFN-gamma. Altogether, these results indicate that SCLC and NSCLC cancer cells can be recognized by autologous CTL, and might therefore be susceptible to specific immunotherapy.

摘要

我们从小细胞肺癌(SCLC)患者和非小细胞肺癌(NSCLC)患者切除的肿瘤材料中获得了肺癌细胞系。NSCLC患者接受了经照射的自体肿瘤细胞疫苗接种。这两名患者的临床病情都得到了格外良好的发展,目前分别在诊断后10年和8年没有癌症迹象。用经照射的自体肿瘤细胞刺激的血液淋巴细胞制备了自体混合淋巴细胞-肿瘤细胞培养物(MLTC)。第一名患者的SCLC细胞携带少量人类白细胞抗原(HLA)I类分子,在用作刺激细胞之前先用γ干扰素(IFN-γ)处理。获得了一个细胞毒性T淋巴细胞(CTL)克隆,该克隆能特异性裂解经IFN-γ处理的SCLC细胞,但不能裂解未处理的肿瘤细胞或自体淋巴母细胞。还获得了针对另一名患者的NSCLC细胞的自体肿瘤特异性CTL克隆。这些肿瘤细胞携带更高水平的HLA I类分子,并且在未经IFN-γ处理的情况下被CTL裂解。总之,这些结果表明SCLC和NSCLC癌细胞可被自体CTL识别,因此可能对特异性免疫疗法敏感。

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