Tumor cells form immune escape and subsequently obtain unlimited proliferation ability due to the abnormal immune surveillance mediated by immune checkpoints. Among this class of immune checkpoints, PD-1/PD-L1 was recognized as an anticancer drug target for many years, and so far, several monoclonal antibodies have achieved encouraging outcome in cancer treatment by targeting the PD-1/PD-L1 signaling pathway. Due to the inherent limitations of antibodies, the development of small molecule inhibitors based on PD-1/PD-L1 signaling pathway is gradually reviving in decades. In this review, we summarized a number of small molecule inhibitors based on three different therapeutic approaches interfering PD-1/PD-L1 signaling pathway: (1) blocking direct interaction between PD-1 and PD-L1; (2) inhibiting transcription and translation of PD-L1; and (3) promoting degradation of PD-L1 protein. The development of these small molecule inhibitors opens a new avenue for tumor immunotherapy based on PD-1/PD-L1 signaling pathway.

由于免疫检查点介导的异常免疫监视，肿瘤细胞形成免疫逃逸，从而获得无限增殖能力。在此类免疫检查点中，PD-1/PD-L1多年来一直被认为是抗癌药物靶点，迄今为止，多种单克隆抗体通过靶向PD-1/PD-L1信号传导在癌症治疗中取得了令人鼓舞的成果途径。由于抗体固有的局限性，基于PD-1/PD-L1信号通路的小分子抑制剂的开发几十年来逐渐复兴。在这篇综述中，我们总结了一些基于三种不同治疗方法干扰PD-1/PD-L1信号通路的小分子抑制剂：（1）阻断PD-1和PD-L1之间的直接相互作用； (2)抑制PD-L1的转录和翻译； (3)促进PD-L1蛋白的降解。这些小分子抑制剂的开发为基于PD-1/PD-L1信号通路的肿瘤免疫治疗开辟了新途径。