妊娠滋养细胞肿瘤（简称GTN）是发生在育龄女性的高度恶性肿瘤，尽管对化疗敏感，仍有部分患者死于化疗耐药和肿瘤广泛转移，找到新的治疗GTN的有效手段是目前亟待解决的问题。基于免疫检查点的免疫治疗是一种新的肿瘤治疗方法。VISTA是新近发现的可以抑制T细胞功能的免疫调节分子。本项目组前期研究发现：VISTA在GTN肿瘤细胞和免疫细胞上均高表达；绒癌细胞株JEG-3上的VISTA抑制T细胞分泌IFN-γ等细胞因子的功能。我们提出以下科学假说：VISTA在GTN中抑制T细胞功能，促进肿瘤免疫逃逸，可能成为GTN的免疫治疗靶点。本项目拟在前期工作基础上，利用基因敲除、抗体阻断等手段体外检测绒癌细胞上的VISTA对肿瘤细胞及T细胞的影响；在免疫系统人源化小鼠体内建立绒癌移植瘤模型，在体内验证VISTA阻断疗法在GTN中的疗效并阐明作用机制，从而为GTN治疗的新方法提供理论依据和新的免疫治疗靶点。

Gestational trophoblastic tumor (GTN) is a highly malignant tumor that occurs in women of childbearing age. Although it is sensitive to chemotherapy, some patients die from chemotherapy resistance and tumor metastasis. Finding new effective methods for treating GTN is an urgent problem to be solved. Immune checkpoint-based immunotherapy is a new approach to cancer therapy. VISTA is a newly discovered immunomodulatory molecule that inhibits T cell function. Previous studies in this project group found that VISTA was highly expressed on both GTN tumor cells and immune cells, VISTA on the choriocarcinoma cell line JEG-3 inhibited the secretion of cytokines such as IFN-γ by T cells. We proposed the following scientific hypothesis: VISTA inhibits T cell function in GTN and promotes tumor immune escape, which may become a target for immunotherapy of GTN. Based on the preliminary work, this project will use the methods of gene knockout and antibody blocking to detect the effect of VISTA on tumor cells and T cells in vitro. On the other hand, the model of choriocarcinoma xenograft will be established in humanized mice to verify the efficacy of VISTA blockade therapy in GTN and to elucidate the mechanism of action of VISTA, thus providing a theoretical basis and a new immunotherapy target for the treatment of GTN.