共抑制分子TIGIT调控CD103+CD8+T细胞在子宫内膜癌肿瘤免疫治疗中的作用及机制研究

子宫内膜癌（EC）是我国发病率最高的妇科肿瘤之一，目前以手术和化疗为主要治疗方式。肿瘤免疫治疗在EC中疗效不尽人意。组织驻留记忆T细胞（TRM）被认为与肿瘤预后相关，但对其调控机制尚不清楚。我们近期研究显示，EC的肿瘤浸润淋巴细胞中存在大量CD103+CD8+TRM聚集，新近发现的抑制性免疫检查点TIGIT与PD-1共同在TRM上显著高表达，TIGIT表达量与肿瘤预后负相关。我们推测TIGIT在TRM耗竭中有重要作用，促进肿瘤进展，可能是EC免疫治疗的新靶点。本课题拟扩大临床样本，深入研究EC中TRM表面TIGIT的表达特点，分析TIGIT对TRM功能及代谢的影响，并结合体外细胞实验、动物实验模型，探讨靶向抑制TIGIT的治疗对逆转耗竭性TRM功能的价值。所得结果将有助于揭示TRM的功能及调控机制，为EC免疫治疗提供新的思路和策略。

Endometrial carcinoma (EC) is a group of gynecological malignancies with the highest incidence in China, the major treatment to which remains surgeries, and chemotherapies. The efficacy of immunotherapy in EC is unsatisfactory. Tissue-resident memory T cells (TRM) are considered to be related to tumor prognosis, but their regulatory mechanisms are not yet clear. Our recent data showed that CD103+ CD8+ tissue-resident memory T cells (TRM) were accumulated in EC-infiltrating lymphocytes. The newly discovered inhibitory immune checkpoint TIGIT，corelated with PD-1，has significantly high expression on TRM. The expression of TIGIT is negatively correlated with tumor prognosis. We speculate that TIGIT plays an important role in TRM exhaustion and promotes tumor progression. TIGIT may be a new target for EC immunotherapy. Based on this, we plan to expand the EC samples size to further study the expression characteristics of TIGIT on the surface of TRM in EC, to analyze the influence of TIGIT on the function and metabolism of this immune subset. In combination with in vitro experiments on both cellular and experimental animal levels, to further explore the value of TIGIT inhibition and its potential in augmenting the anti-tumor effect of CD103+ CD8+ TRM. Eventual outcomes from this study will benefit elucidating the function and mechanism of CD103+ CD8+ TRM and will provide novel strategies and approaches of immunotherapy to EC.