PTGES调节G-CSF分泌在肺腺癌微环境中的作用和调控机制

阐明肺腺癌发生和转移的分子机理是当前肺腺癌研究的重点和难点。炎症与肺腺癌的发生和转移紧密相关，但具体机制尚不清楚。通过对我们前期进行的小鼠尾静脉接种肺腺癌细胞转移实验、细胞系mRNA表达谱分析及细胞培养上清液的细胞因子检测，我们提出“PTGES/AKT/G-CSF通路能够调控肺腺癌微环境促进肺腺癌的发生和转移”的科学假说。我们将进一步明确肺腺癌细胞炎症反应对肿瘤微环境中免疫细胞的调控作用，并拟在细胞、小鼠和肺腺癌临床样本三个层面上阐明：①PTGES对肺腺癌自发和转移的重要性；②PTGES调控肺腺癌免疫微环境的分子机制；③靶向PTGES联合PD-L1抗体治疗能够阻断免疫逃逸。本课题的实施将深化PTGES通过AKT/G-CSF这一信号通路调控肺腺癌发生和转移的认识，并能为抑制肺腺癌的发生和转移开拓新思路，明确其临床转化意义为肺腺癌分类、预后判断和治疗提供新的理论依据。

The most important and difficult point of lung adenocarcinoma (LADC) research is to clarify the mechanism of LADC spontaneous and metastasis. Inflammation is strongly related to LADC spontaneous and metastasis, but the molecular mechanism remains to be elucidated. Through tail vein injection of LADC cells in mice, cells mRNA seq analysis and cytokine detection of tumor cells conditioned medium, we hypothesize that “the PTGES/AKT/G-CSF pathway can regulate the tumor microenvironment to promote the occurrence and metastasis of LADC”. We will further clarify the regulation of LADC inflammation on immune cells in the tumor microenvironment, and plan to clarify at the three levels of cells, mice, and LADC clinical samples. In this proposal, we are going to study three specific aims: ①The importance of PTGES to LADC spontaneous and metastasis; ②The mechanism of PTGES regulating the immune microenvironment of LADC; ③Targeting PTGES combined with PD-L1 antibody therapy can inhibit immune escape. We will explain that PTGES regulates the spontaneous and metastasis of LADC through the AKT/G-CSF signaling pathway, and can open up new ideas for inhibiting the spontaneous and metastasis. This will elucidate its clinical translation significance and provide a new strategy for the classification, prognosis judgment and treatment of LADC.