Induction of T cell-mediated immune response by dendritic cells pulsed with mRNA of sphere-forming cells isolated from patients with gastric cancer
Induction of T cell-mediated immune response by dendritic cells pulsed with mRNA of sphere-forming cells isolated from patients with gastric cancer
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DOI：
10.1016/j.lfs.2019.01.016
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发表时间：
2019-02-15
期刊：
影响因子：
6.1
通讯作者：
Gholamin, Mehran
中科院分区：
文献类型：
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作者：
Bagheri, Vahid;Abbaszadegan, Mohammad Reza;Gholamin, Mehran
胃癌（GC）作为全球癌症相关死亡的第三大常见原因，是异质性非常高的癌症之一。癌症干细胞（CSC）作为实体瘤中癌细胞的一小部分，具有自我更新、分化和致瘤能力，负责肿瘤的发生、进展、复发、转移和对当前治疗的抵抗。因此，根除CSC对于治愈癌症至关重要。在这里，我们首先分离并鉴定了四名胃癌患者肿瘤组织中的球体形成细胞，然后从干扰素γ（IFN-γ）基因表达和特异性细胞毒性方面分析了负载球体形成细胞总mRNA的单核细胞源性树突状细胞（DC）诱导的T细胞反应。在无血清培养基中形成球状集落。从肿瘤球中分离出来的球形成细胞异质表达 CD44、CD54 和上皮细胞粘附分子 (EpCAM) 标记物，并在裸鼠中产生一种肿瘤。这些结果表明胃CSC在肿瘤球中富集。经过 12 天的共培养后，负载有球形成细胞 mRNA 的细胞因子成熟 DC 能够诱导 T 淋巴细胞中的 IFN-γ 基因表达。与转染正常组织的DC刺激的T淋巴细胞相比，这些淋巴细胞中IFN-γ基因的mRNA水平表达更高（6.4-9.39倍）。带有球形成细胞抗原的致敏 T 淋巴细胞的细胞毒活性显着高于正常组织抗原和模拟 DC（P
Gastric cancer (GC) as the third most common cause of cancer-associated mortality worldwide is one of the cancers with very high heterogeneity. Cancer stem cells (CSCs) as a small subset of cancer cells in solid tumors with the self-renewal, differentiation and tumorigenic ability are responsible for tumor initiation, progression, recurrence, metastasis, and resistance to current treatments. Therefore, eradication of CSCs is very vital to cure cancer. Here, we first isolated and identified sphere-forming cells in tumor tissue from four GC patients and then analyzed T cell responses induced by monocyte-derived dendritic cells (DCs) loaded with total mRNA of sphere-forming cells in terms of interferon-gamma (IFN-gamma) gene expression and specific cytotoxicity. Spheroid colonies were formed in serum-free media. Sphere-forming cells dissociated from tumorspheres heterogeneously expressed CD44, CD54, and epithelial cell adhesion molecule (EpCAM) markers and generated one tumor in nude mice. These results demonstrated that gastric CSCs were enriched in tumorspheres. Cytokine-matured DCs loaded with mRNA of sphere-forming cells were able to induce IFN-gamma gene expression in T-lymphocytes after a 12-day co-culture. mRNA level of IFN-gamma gene in these lymphocytes was more highly expressed compared to stimulated T-lymphocytes by DCs transfected with normal tissue (6.4-9.39 folds). Cytotoxic activity of primed T-lymphocytes with antigens of sphere-forming cells was significantly higher than normal tissue antigens and mock DCs (P