猕猴桃根多糖抑制PD-1/PD-L1信号通路调控巨噬细胞极化阻抑胃癌转移侵袭的作用机制研究

复发转移是影响胃癌临床疗效关键，靶向肿瘤微环境是抑制胃癌转移侵袭的重要途径。肿瘤微环境中肿瘤相关巨噬细胞（TAMs）M1型极化可有效抑制肿瘤，程序性死亡受体-1（PD-1）缺失促进TAMs M1型转化。中医药可提高机体免疫力，改善肿瘤微环境。项目组在2个国自然及其他项目研究基础上，发现中药猕猴桃根多糖（AEPS）可抑制胃癌侵袭转移，下调瘤块PD-1表达，促进CD8+T淋巴细胞浸润，提高TAMs中M1-TAMs含量，提示AEPS可调控胃癌肿瘤微环境抑制胃癌转移。据此我们提出假说“AEPS通过抑制PD-1/PD-L1信号通路激活，调控炎症因子释放，促进TAM向M1型极化，重塑胃癌微环境，从而抑制胃癌的侵袭转移”。本项目拟运用流式、组织芯片、液相芯片、转录组测序、动物活体成像等技术，部分阐明AEPS重塑胃癌微环境抑制胃癌的侵袭转移的机制。项目的实施将为中医药防治胃癌复发转移提供免疫治疗新策略。

Recurrence and metastasis is the key to the clinical efficacy of gastric cancer. Targeting the tumor microenvironment is a important way to inhibit tumor metastasis. Tumor associated macrophage (TAMs) is an component of the microenvironment, the absence of procedural death receptor-1 (PD-1) promoting the TAMs transform to M1 type. Traditional Chinese medicine can strength the immunity and improve the tumor microenvironment. Based on the preliminary researches supported by China national natural science foundation and other project, we found that Actinidia eriantha polysaccharide (AEPS) can inhibits the invasion and metastasis of gastric cancer, reduces PD-1 expression, improves CD8+T lymphocyte infiltration, increases the proportion of M1-TAMs, indicates that AEPS can regulates tumor microenvironment and inhibits gastric cancer metastasis. Accordingly we propose a hypothesis: “AEPS can inhibits the activation of PD-1/PD-L1 signaling pathway, regulates inflammatory cytokines, promotes the polarization of TAM to M1 type, reshape the microenvironment, by which means inhibits the invasion and metastasis of gastric cancer”. In this study we intend to collect samples from animals, cells and clinical level, apply techniques such as flow cytometry, organization chip, liquid phase chip, transcriptome sequencing and living animal imaging, to partly reveal the mechanism of AEPS in inhibiting gastric cancer invasion and metastasis by remolding tumor microenvironment. This project will provide a new strategy of immunotherapy in inhibiting gastric cancer metastasis by traditional Chinese medicine.