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首页> 外文期刊>Clinical cancer research: an official journal of the American Association for Cancer Research >Cyclin D1-specific cytotoxic T lymphocytes are present in the repertoire of cancer patients: implications for cancer immunotherapy.
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Cyclin D1-specific cytotoxic T lymphocytes are present in the repertoire of cancer patients: implications for cancer immunotherapy.

机译：Cyclin D1特异性细胞毒性T淋巴细胞存在于癌症患者库中：对癌症免疫疗法的意义。

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PURPOSE: Cyclin D1, a key cell cycle regulator, is overexpressed in multiple types of cancer. Such tumor-associated genes may be useful targets for cancer immunotherapy. Nevertheless, it had previously been suggested that efficient T cells recognizing cyclin D1-derived epitopes are absent from the repertoire because of thymic deletion. We attempted to induce autologous CTL from healthy donors and patients with cyclin D1-overexpressing tumors using a highly efficient T-cell expansion system based on CD40-activated B cells as antigen-presenting cells. EXPERIMENTAL DESIGN: Cyclin D1-derived, HLA-A*0201-restricted epitopes were predicted by multiple computer algorithms, screened in HLA-A2-binding assays, and used for T-cell stimulation. The generated CTL lines and clones were analyzed by IFN-gamma enzyme-linked immunosorbent spot assay or cytolysis assay. RESULTS: After screening, at least two naturally processed and presented HLA-A*0201-binding cyclin D1 epitopes were identified. CTL specific for these epitopes could be successfully generated from HLA-A2(+) donors. T cells efficiently recognized target cells pulsed with the cognate peptide and cyclin D1-expressing tumor cell lines in an HLA-A*0201-restricted manner. More importantly, HLA-A*0201-matched, primary cyclin D1(+) tumor cells were efficiently recognized by cyclin D1-specific CTL. These CTL could be generated from patients with mantle cell lymphoma and cyclin D1(+) colon cancer. CONCLUSIONS: These results underscore that cyclin D1 needs to be considered as a target for broad-based antitumor immunotherapy.
机译：目的：Cyclin D1是一种关键的细胞周期调节剂，在多种类型的癌症中均过表达。此类肿瘤相关基因可能是癌症免疫治疗的有用靶标。然而，以前曾有人提出，由于胸腺缺失，有效的T细胞无法识别细胞周期蛋白D1衍生的表位。我们尝试使用基于CD40激活的B细胞作为抗原呈递细胞的高效T细胞扩增系统，从健康供体和过度表达细胞周期蛋白D1的肿瘤患者中诱导自体CTL。实验设计：通过多种计算机算法预测细胞周期蛋白D1衍生的HLA-A * 0201限制性表位，并在HLA-A2结合试验中进行筛选，并用于T细胞刺激。通过IFN-γ酶联免疫斑点测定或细胞溶解测定法分析产生的CTL系和克隆。结果：筛选后，至少鉴定了两个自然加工并呈递的结合HLA-A * 0201的细胞周期蛋白D1表位。可以从HLA-A2（+）供体成功生成针对这些表位的CTL。 T细胞以HLA-A * 0201限制的方式有效地识别了表达同源肽和表达细胞周期蛋白D1的肿瘤细胞系。更重要的是，细胞周期蛋白D1特异性CTL有效识别HLA-A * 0201匹配的原发性细胞周期蛋白D1（+）肿瘤细胞。这些CTL可能来自有套细胞淋巴瘤和细胞周期蛋白D1（+）结肠癌的患者。结论：这些结果强调细胞周期蛋白D1需要被认为是广泛的抗肿瘤免疫治疗的靶标。

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