肿瘤源性清道夫受体阳性微颗粒（ScR+MPs）介导树突状细胞耐受：甲状腺癌免疫逃逸新机制

项目名称： 肿瘤源性清道夫受体阳性微颗粒（ScR+MPs）介导树突状细胞耐受：甲状腺癌免疫逃逸新机制

项目编号： No.81502322

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 李大鹏

作者单位： 天津医科大学

项目金额： 18万元

中文摘要： 微颗粒（MPs）是新近发现的细胞间通讯的信息传递载体，是不同细胞相互调节的新方式。申请者先期报道了表达Toll样受体（TLR）的肿瘤细胞通过释放MPs向树突状细胞（DC）传递microRNA，最终调节DC炎症表型。新近文献指出，清道夫受体（ScR）介导的DC胞内脂类代谢异常是导致DC免疫应答能力下降的重要原因。ScR表达于部分肿瘤表面并可被MPs装载，我们猜想：肿瘤可否利用MPs传递自身ScR至DC并影响其脂类代谢过程，最终导致免疫逃逸？我们近期报导了TLR3在甲状腺癌表达并与颈部淋巴结转移显著相关，并发现甲状腺癌在TLR3刺激下释放ScR+MPs增多，提示甲状腺癌可能利用MPs传递ScR介导DC免疫抑制并发生转移。本课题通过构建表达荧光ScR甲状腺癌细胞株并观察ScR在体内体外环境下的传递过程，验证传递后DC免疫功能改变，揭示肿瘤免疫逃逸新机制，为甲状腺癌免疫治疗提供可能的新方向。

中文关键词： 甲状腺和甲状旁腺肿瘤；甲状腺乳头状癌；微颗粒；清道夫受体；免疫逃逸

英文摘要： Microparticles (MPs) are newly identified mediators for intercellular communications by which regulation of cells from different origins, induction and education of cells could be achieved. We have previously reported that tumor cells expressing Toll-like receptor (TLR) release MPs encapsulating miRNAs to dendritic cells to down-regulate their inflammatory pattern. Recent studies showed that scavenger receptor (ScR) mediates abnormal lipid transfer, leading to immune-irresponsiveness of DC. Considering ScR is expressed on tumor cells and could be loaded and transferred via MPs, we postulate that tumor might shed ScR to DC via MPs releasing and down-regulate DC lipid metabolism, leading to immune evasion. Our recent study indicated that TLR3 is expressed on papillary thyroid carcinoma and correlated with cervical lymph node metastasis. We also found that ScR+MPs releasing is enhanced by TLR3 stimulation in PTC cells, which suggests that thyroid carcinoma might exert immunosuppression to DC via ScR+MPs thus leading to metastasis. GFP-tagged ScR vector is to be used to construct thyroid carcinoma cells expressing GFP-ScR. In vivo and in vitro studies are designed to verify the ScR transferring from tumor to DC, thus unveiling the novel mechanism of tumor evasion, and providing new directions for the immunotherapy for thyroid carcinoma.

英文关键词： thyroid and parathyroid tumor;papillary thyroid cancer;microparticle;scavenger receptor;immune evasion