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Characterization of human prostate and breast cancer cell lines for experimental T cell-based immunotherapy

机译:基于实验性T细胞免疫疗法的人前列腺和乳腺癌细胞系的表征

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摘要

BACKGROUND. In order to develop experimental immunotherapy for prostate and breast cancer it is of outmost importance to have representative target cell lines that through human leukocyte antigen (HLA) class I molecules present relevant levels of peptides from tumor-associated antigens for cytotoxic T lymphocyte (CTL) recognition. METHODS. We sequenced the HLA-A and HLA-B loci of eight commonly used prostate and breast cancer cell lines and analyzed the surface expression of HLA-ABC, HLA-DR, CD40, CD80, CD86, and CD54 by flow cytometry. We also analyzed the cell lines for mRNA expression from 25 genes reported to be specifically or preferentially expressed by prostate cells. RESULTS. Among the analyzed cell lines we found that LNCaP, PC-346C and MCF-7 are HLA-A*0201 positive. However, the HLA-A2 expression level is low and only MCF-7 upregulates HLA-A2 in response to IFN-γ stimulation. MCF-7 also expresses high levels of CD54, which further improve its value as a CTL target cell line. On the other hand, LNCaP and PC-346C express 25 and 23 out of 25 prostate-related genes, respectively, while MCF-7 expresses 16 out of 25 genes. CONCLUSIONS. None of the analyzed prostate cancer cell lines are optimal CTL target cells. However, MCF-7 could in many cases be used as a complement to HLA-A*0201 positive prostate cancer cells. The LNCaP and PC-346C cell lines are rich sources of prostate-related antigens that may be valuable for cancer vaccine development.
机译:背景。为了开发针对前列腺癌和乳腺癌的实验性免疫疗法,具有代表性的靶细胞系至关重要,该靶标细胞系通过人白细胞抗原(HLA)I类分子呈现出与肿瘤相关抗原相关的肽水平,以用于细胞毒性T淋巴细胞(CTL)承认。方法。我们对八种常用前列腺和乳腺癌细胞系的HLA-A和HLA-B基因座进行了测序,并通过流式细胞术分析了HLA-ABC,HLA-DR,CD40,CD80,CD86和CD54的表面表达。我们还分析了据报道由前列腺细胞特异性或优先表达的25个基因的mRNA表达的细胞系。结果。在分析的细胞系中,我们发现LNCaP,PC-346C和MCF-7为HLA-A * 0201阳性。但是,HLA-A2表达水平较低,并且只有MCF-7会响应IFN-γ刺激而上调HLA-A2。 MCF-7还表达高水平的CD54,这进一步提高了其作为CTL靶细胞系的价值。另一方面,LNCaP和PC-346C分别表达25个前列腺相关基因中的25个和23个,而MCF-7表达25个前列腺相关基因中的16个。结论。分析的前列腺癌细胞系都不是最佳的CTL靶细胞。然而,在许多情况下,MCF-7可以用作HLA-A * 0201阳性前列腺癌细胞的补充。 LNCaP和PC-346C细胞系是前列腺相关抗原的丰富来源,可能对癌症疫苗的开发很有价值。

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