健脾益气中药通过调节肠道菌群对肺癌PD-1/PD-Ls信号通路相关免疫抑制微环境干预机制的研究

近年来针对肺癌PD-1/PD-Ls通路的免疫检查点抑制剂的治疗取得了突破性的进展，而肠道菌群的变化与其疗效密切相关。前期工作证实扶正中药对肺癌免疫抑制微环境具有调控的作用，我们提出健脾益气中药可通过调节机体肠道菌群而对肺癌PD-1/PD-Ls信号通路相关免疫抑制微环境起到干预作用的工作假说。我们以四君子汤及其君药人参提取物（人参皂甙Rg3）为代表药，以澳大利亚弗林德斯大学已建立的“16S rRNA多引物-多变异区微生物组学”测序策略为主要研究方法，观察：①不同肠道菌群状态荷瘤机体PD-1/PD-Ls信号通路相关免疫抑制微环境的状态，中药及PD-1抑制剂以及两者相协同对其的影响；②中药及PD-1抑制剂以及两者相协同对不同肠道菌群状态机体肺癌生长与转移的影响；③脾气虚证与非脾气虚证Ⅳ期非小细胞肺癌患者肠道菌群结构的异同及其与血sPD-L1水平的关系，中药对此在不同时间点的调节作用。

In recent years, breakthroughs have been made in the treatment of lung cancer PD-1 / PD-Ls pathway immune checkpoint inhibitors, and changes in the intestinal flora are closely related to their efficacy. The previous work confirmed that Fuzheng Chinese medicine has a regulatory effect on the lung cancer immunosuppression microenvironment. We propose that Jianpi Yiqi Traditional Chinese medicine can play a role in the lung cancer PD-1 / PD-Ls signaling pathway-related immune suppression microenvironment by regulating the body ’s intestinal flora The working hypothesis of the role of intervention. We take Sijunzi Decoction and its ginseng extract (Ginsenoside Rg3) as representative drugs, and take the “16S rRNA multi-primer-multivariable region microbiome” sequencing strategy established by Flinders University in Australia as the main research method. Observation: ① The state of the immunosuppressive microenvironment related to the PD-1 / PD-Ls signaling pathway in tumor-bearing organisms with different intestinal flora, the effect of Chinese medicine and PD-1 inhibitors and the synergy between them; ② Chinese medicine and PD -1 inhibitors and the synergy between the two on the growth and metastasis of lung cancer in different intestinal flora; ③Spleen Qi deficiency syndrome and non-spleen Qi deficiency syndrome Stage IV non-small cell lung cancer patients with similarities and differences in intestinal flora structure and The relationship between blood sPD-L1 level and the regulatory effect of traditional Chinese medicine on this at different time points.