微波消融治疗对肝细胞癌小鼠髓源性抑制细胞和免疫微环境的影响及机制探讨

Hepatocellular carcinoma is the 2nd mortal disease in malignant tumors and threatens human health seriously. The occurrence and development of tumor is related to tumor cells evading the host’s immune response. Features common to all myeloid derived suppressor cells (MDSCs) are their myeloid origin, immature state and a remarkable ability to suppress T-cell responses. MDSCs have recently been recognized as a subset of innate immune cells that can alter adaptive immunity and produce immunosuppression. MDSCs have been reported to comprise a group of heterogeneous immature myeloid cells, which have suppressive biological activities as a common denominator. MDSCs regulate both acquired and innate immunity by direct or indirect pathways. To exert their immunosuppressive function in tumor-bearing hosts, MDSCs are required to expand in lymphoid organs and are subsequently recruited to the tumor site. It is an effective method of microwave ablation in treatment of hepatic cancer. Microwave ablation could promote the body to generate immune response. In the study, we observed the MDSCs changes and trends in tumor site and tumor microenvironment, and changes of the level of IL1, IL4, IL13, IFNγ, ARG-1 and iNOS, and the activity of STAT1 and STAT6. Then we investigate interactions mode and way of MDSCs and hepatocellular carcinoma cells. To research the possible mechanism of microwave ablation in MDSCs mediated immunomodulation role of hepatocellular carcinoma from the organ, tissue and cell three levels. To provide clinical experimental and theoretical basis for study of immune response in hepatocellular carcinoma microwave ablation.

肝细胞癌年死亡率高居恶性肿瘤死亡率的第二位，是严重威胁人类身体健康的致死性疾病。肿瘤的发生发展同肿瘤细胞逃逸机体的免疫监视有关。髓源性抑制细胞（MDSCs）可以通过多种途径抑制机体的获得性和天然抗肿瘤免疫，使肿瘤细胞逃避机体的免疫监视和攻击，促使肿瘤发展。微波消融治疗肝细胞癌疗效确切且能够促进机体产生免疫反应。本项目通过对比分析微波消融治疗对肝细胞癌小鼠MDSCs在肿瘤及肿瘤微环境中的变化及趋势，观察体内外肝癌环境中MDSCs转化相关的细胞和免疫因子的变化、可能信号转导通路相关蛋白的表达及磷酸化水平的改变、以及肿瘤微环境中的ARG-1和iNOS含量的变化过程，研究MDSCs与肝细胞癌相互作用的方式及途径，从器官、组织和细胞三个层次阐述微波消融后MDSCs变化过程及其影响免疫过程的可能机制，探讨微波消融改善免疫抑制的新途径，为肝细胞癌微波消融治疗的免疫功能研究提供临床实验依据和理论基础。