Junking Mutita, Grainok Janya, Thepmalee Chutamas, Wongkham Sopit, Yenchitsomanus Pa-Thai
1 Division of Molecular Medicine, Department of Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
2 International Graduate Programs in Medical Biochemistry and Molecular Biology, Department of Biochemistry, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
Tumour Biol. 2017 Oct;39(10):1010428317733367. doi: 10.1177/1010428317733367.
Cholangiocarcinoma is a malignancy of bile duct epithelia with an increasing in incidence rate worldwide. Surgery is the only curative treatment, while adjuvant chemotherapy and radiotherapy render poor responses. Cell-based immunotherapy is a potential strategy for cholangiocarcinoma treatment. However, variation of tumor antigens in cholangiocarcinoma leads to the ineffectiveness of cell-based immunotherapy. In this study, we examined the activation of effector T-cells by dendritic cells pulsed with protein lysate or total RNA from cholangiocarcinoma cell lines for their cytolytic activity against cholangiocarcinoma. Broad-spectrum antigen types with respect to RNA antigen sources were obtained from combination of three cholangiocarcinoma cell lines (KKU-213, KKU-100, and KKU-055). Compared with protein lysate-pulsed dendritic cells, total RNA-pulsed dendritic cells induced anti-tumor effector T-cell response with higher killing ability to KKU-100 and KKU-213 cells compared with protein lysate-pulsed dendritic cells. Moreover, pooled messenger RNA from three cholangiocarcinoma cell lines significantly increased the specific killing capacity of activated lymphocytes against KKU-213 cells. These results suggest that activation of anti-tumor effector T-cells against cholangiocarcinoma by RNA-pulsed dendritic cells is more effective than that by protein lysate-pulsed dendritic cells. In addition, pulsing dendritic cells with pooled messenger RNA from multiple cell lines enhanced the efficacy of a cellular immune response against cholangiocarcinoma.
胆管癌是一种胆管上皮恶性肿瘤，在全球范围内发病率呈上升趋势。手术是唯一的治愈性治疗方法，而辅助化疗和放疗效果不佳。基于细胞的免疫疗法是治疗胆管癌的一种潜在策略。然而，胆管癌中肿瘤抗原的变异导致基于细胞的免疫疗法无效。在本研究中，我们检测了用胆管癌细胞系的蛋白裂解物或总RNA脉冲处理的树突状细胞对效应T细胞的激活情况，以观察其对胆管癌的细胞溶解活性。通过三种胆管癌细胞系（KKU-213、KKU-100和KKU-055）的组合，获得了关于RNA抗原来源的广谱抗原类型。与用蛋白裂解物脉冲处理的树突状细胞相比，用总RNA脉冲处理的树突状细胞诱导的抗肿瘤效应T细胞反应对KKU-100和KKU-213细胞的杀伤能力更强。此外，来自三种胆管癌细胞系的混合信使RNA显著提高了活化淋巴细胞对KKU-213细胞的特异性杀伤能力。这些结果表明，用RNA脉冲处理的树突状细胞激活针对胆管癌的抗肿瘤效应T细胞比用蛋白裂解物脉冲处理的树突状细胞更有效。此外，用来自多个细胞系的混合信使RNA脉冲处理树突状细胞可增强针对胆管癌的细胞免疫反应的疗效。
