肿瘤免疫疗法是目前肿瘤治疗的热点，特别是免疫检查点PD-1/PD-L1抑制剂显示出了突破性的治疗效果。冬虫夏草兼有免疫调控及抗肿瘤的疗效，然物质基础尚不明确。申请者前期通过靶标筛选发现其乙酸乙酯部位与PD-1、PD-L1具有显著的亲和力，细胞实验也显示该部位能有效阻断PD-1和PD-L1之间的结合。基于中医肿瘤学“扶正固本”的治则，结合冬虫夏草功用，申请人提出“冬虫夏草中阻断PD-1/PD-L1的化学成分（群）可能是其发挥抗肿瘤疗效的重要物质基础”假说。本项目拟构建靶向PD-1/PD-L1的配体垂钓体系，迭代垂钓活性部位中与靶标有特异性亲合的成分，以HPLC-MS检测和定位分析垂钓成分为指导，靶向分离、鉴定其中目标成分（群），并进行亲和力验证及基于体内外肿瘤模型的药效评价，以期获得目标活性成分（群）。在探索冬虫夏草药效物质基础的同时，提供免疫治疗学视角的冬虫夏草抗肿瘤物质的发掘方案。

The antineoplastic strategy of enhancing the body's immunity is a hot spot among current cancer therapies, and drugs with the abilities of inhibiting the programmed death 1 (PD-1) and programmed death ligand 1 (PD-L1) also showed significant therapeutic effects. Though the immunomodulatory and anti-tumor effects of Cordyceps sinensis were well confirmed, their material basis is still not clear so far. Our early SPR and cell experiments suggested that the ethyl acetate extract of Cordyceps sinensis had significant affinity with the tumor immunological checkpoints PD-1 and PD-L1. Followed the idea of "Fuzheng Guben" in traditional Chinese medicine oncology and combined with the function of Cordyceps sinensis, this study predicts that "those chemical constitutes (group) blocking PD-1/PD-L1 in Cordyceps sinensis may be account for its anti-tumor effect." In this project, we propose to construct an iterative ligand fishing system targeting PD-1/PD-L1. Guided by the results of SPR experiments and HPLC-MS profiles, target components (groups) will be isolated and elucidated, and their abilities of affinity and activity also will be verified based on tumor models in vitro and in vivo. Besides obtaining the target active ingredients (groups) and exploring the material basis, this research tries to provide a solution for the anti-tumor constituents' excavation from a perspective of immunotherapeutics.