靶向阻断Tim-3/Galectin-9信号介导的免疫逃逸抑制黑色素瘤的作用及机制研究

Tim-3表达于多种免疫细胞表面，Tim-3/Gal-9信号可抑制Th17细胞功能,促进CD8+T细胞凋亡。同时，肿瘤微环境中内皮细胞表面的Tim-3分子与B16细胞的某分子衔接，可促进其增殖和抗凋亡作用，但其机制尚不清楚。我们前期研究发现Tim-3/Gal-9信号在肿瘤的发生发展及其免疫逃逸发挥着极为重要的作用。基于此，本课题设计以黑色素瘤细胞株及黑色素瘤动物模型为研究对象，通过体内外实验探讨Tim-3/Gal-9信号对黑色素瘤肿瘤细胞增殖、凋亡、转移及免疫逃逸的影响，同时研究基于海藻酸盐水凝胶靶向阻断Tim-3/Gal-9信号通路恢复肿瘤特异性DC和Th17细胞抗肿瘤功能的免疫机制，并结合临床标本分析Tim-3/Gal-9信号调控肿瘤特异性DC和Th17细胞与黑色素瘤发生发展的关系，从而揭示其在促进黑色素瘤增殖与肿瘤免疫逃逸中的双重促瘤作用及机制，为以其为靶点的肿瘤干预策略提供新思路。

Tim-3 expression on the surface of a variety of immune cells Tim-3/Gal-9 signal suppressed Th17 cell function, promote CD8 + T cell apoptosis, play an important role in the progression of tumors, infections and other diseases.We found Tim-3/Gal-9 signal plays an important role in tumor development and immune escape.Melanoma cell lines, melanoma tumor-bearing mouse model and alginate hydrogelsl will be used of our study to explore the Tim-3/Gal-9 signal melanoma tumor cell proliferation, apoptosis， metastasis and immune escape in vitro and in vivo experiments and antitumor immune mechanisms of restoration of tumor-specific DC and Th17 cells, meanwhile, analyze the relations between Tim-3/Gal-9 signal regulation of tumor-specific DC and Th17 cells and melanoma development with clinic specimens to reveal the two pro-tumor effect and mechanism that promotion of the proliferation and immune escape of melanoma, and to provide new ideas and a new target for cancer intervention strategies.