肺癌细胞表面CALR-TLR4复合体趋化DCs迁移并诱导其成熟激活抗肿瘤免疫反应抑制肺癌进展的机制研究

肺癌是严重危害人类健康的恶性肿瘤之一，其发病率和死亡率位居所有肿瘤之首。尽管目前已有研究表明钙网蛋白CALR是免疫原性凋亡肺癌细胞的表面抗原，与机体的抗肿瘤免疫密切相关，然而其在抗肿瘤免疫中的具体机制尚不明确。申请人前期研究发现，肺癌细胞表面CALR对树突状细胞（DCs）具有趋化和诱导成熟的作用，可以抑制肿瘤的进展；CALR可与TLR4相互作用并促进其表达；同时，细胞表面高表达CALR的肺癌组织浸润的DCs较多，且患者预后较好。鉴于此，本课题从肺癌细胞表面CALR与DCs浸润的关系出发，探究CALR-TLR4复合体趋化DCs迁移并诱导其成熟的功能及分子机制，并深入探讨CALR-TLR4复合体趋化DCs迁移并诱导其成熟对肺癌进展的抑制作用。本项目的实施，预期将为CALR-TLR4复合体在诱导肺癌细胞免疫原性凋亡的作用提供实验依据，旨在为临床中肺癌的免疫治疗提供理论依据和思路。

Lung cancer is one of the common malignant tumors which threaten human life, with high morbidity and mortality. It has been reported that calreticulin (CALR) is a surface antigen of immunogenic apoptotic lung cancer cells, which is closely related to the body's anti-tumor immunity, but the specific mechanism of CALR in anti-tumor immunity is still unclear. Our previous research found that CALR on the surface of lung cancer cells (mCALR) had chemotactic and induced maturation effects on dendritic cells (DCs) and could inhibit tumor progression; CALR could interact with TLR4 and promoted its expression; in the meanwhile, the expression of mCALR was positively related with DCs infiltration in lung cancer tissues and good prognosis in patients with lung cancer. Therefore, based on the relationship between mCALR and DCs infiltration, this study explores the function and mechanism of CALR-TLR4 complex in DCs chemotaxis and maturity and investigates the inhibitory effect of CALR-TLR4 complex on lung cancer progression. The implementation of this project is expected to provide experimental evidence for the role of CALR-TLR4 complex in inducing the immunogenic apoptosis of lung cancer cells, providing theoretical basis and ideas for immunotherapy of lung cancer.