全球肺癌居于癌症发病率以及病死率首位，我国近年呈上升趋势。以免疫共刺激因子PD-1/PD-L1靶向治疗为代表，非小细胞肺癌免疫治疗取得较大进展。肿瘤免疫相关机制中肿瘤微环境浸润的巨噬细胞是其关键环节之一。巨噬细胞可分为M1型激活免疫应答发挥抗肿瘤作用， M2型诱导免疫耐受有促肿瘤作用。既往研究表明巨噬细胞向M2型转化与肿瘤免疫逃逸促恶性进展相关。ABCG1为跨膜蛋白调控胆固醇外流，该基因缺乏引起细胞内胆固醇堆积促进巨噬细胞向M1型转换。本项目拟研究ABCG1介导巨噬细胞极化在非小细胞肺癌侵袭转移的作用机制，体内及体外实验结合，采用慢病毒载体过表达及沉默策略技术、基因敲除动物模型、临床样本中评价其与非小细胞肺癌恶性进展的相关性。并予调控细胞内胆固醇水平，阐明ABCG1、胆固醇水平、巨噬细胞极化在肿瘤免疫的网络机制，调控该机制对PD-1抑制剂敏感性的影响，为临床转换研究奠定理论基础。

Globally, lung cancer ranks the most frequently diagnosed cancer and the major cause of cancer-related mortality. The incidence of lung cancer in our country keeps rising in recent years. Human immune-checkpoint-inhibitor antibodies inhibit the PD-1 receptor or PD-L1, which improves antitumor immunity. In the latest progress of cancer immunology, tumor-associated macrophage was proved to play a key role in the tumor microenvironment. Tumor-associated macrophages could polarize towards an inflammatory ‘M1’ or a pro-tumor ‘M2’ state, depending on their environmental stimuli. ABCG1 effluxes excess cholesterol to high-density lipoprotein particles for reverse cholesterol transport, which is an essential path to the elimination of intercellular cholesterol. It is reported that Abcg1 knockout mice exhibited massive accumulation of neutral lipids and phospholipids in macrophages which correlate to ‘M1’ state. In the present study, we aim to investigate the ability of ABCG1 mediates the tumor-associated macrophage polarization in the mechanism of non-small cell lung cancer invasion and migration, which may provide new insights in cancer biology and evidence for future clinical practice.