抗PD-1/PD-L1免疫治疗已成晚期非小细胞肺癌（NSCLC）治疗的热点，但目前在临床实践中存在很大的局限性。我们前期研究发现NSCLC组织样本中法尼酯X受体FXR与PD-L1表达存在明显负相关，体外抑制FXR可上调NSCLC中PD-L1表达，而过表达 FXR 则下调 PD-L1的表达。本课题从FXR调控肿瘤免疫反应的功能视角出发，体内验证FXR低表达动物通过上调PD-L1表达，而引起的对PD-L1抗体反应率增强、肿瘤生长受抑的效应；同时采用肿瘤细胞与免疫细胞共培养体系、干扰或过表达手段结合临床样本，考察FXR在肿瘤免疫微环境中对肿瘤细胞和免疫细胞功能表型的调控作用，进一步明确FXR调控PD-L1表达对抗肿瘤免疫治疗的作用，并探讨具体的分子机制。本研究有助于优化和拓宽PD-1/PD-L1免疫治疗的最佳受益人群。

Anti-PD-1/PD-L1immunotherapy has been a hot topic for the treatment of advanced non-small cell lung cancer (NSCLC). However, there are significant limitations in clinical practice. Our previous study found that there was a significant negative correlation between farnesoid X receptor (FXR) and PD-L1 expression in NSCLC tissue samples. In vitro experiments revealed that FXR down-regulation promoted the expression of PD-L1 in NSCLC cells, while FXR over-expression reduced PD-L1 expression. This research will be conducted from the perspectives of the regulatory effects of FXR on tumor immune response to clarify the role of FXR in regulating PD-L1 expression in the tumor immunotherapy. We will further validate that the animals with decreased expression of FXR enhanced the PD-L1 antibody response rate by up-regulating the expression of PD-L in lung cancer tissues, thereby achieving the goal of inhibiting tumor growth. Meanwhile, we will use co-culture system, gene interference or over-expression technologies in vivo and in vitro as well as clinical correlation research to investigate the influence of FXR on immune response, related immune cells and inflammatory cytokins and their molecular modulation mechanisms in NSCLC. This study will help reveal the synergistic effect of targeted FXR against tumor immunotherapy, to optimize and enrich the optimal population suitable for anti-PD-1/PD-L1 immunotherapy, and to clarify the regulating effects of FXR on NSCLC immune reaction and their mechanisms.