NHC Key Laboratory of Carcinogenesis (Central South University) and Hunan Key Laboratory of Translational Radiation Oncology, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410013, Hunan, China.
The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute and School of Basic Medical Science, Central South University, Changsha, 410078, China.
Mol Cancer. 2019 Jan 15;18(1):10. doi: 10.1186/s12943-018-0928-4.
Tumor immune escape is an important strategy of tumor survival. There are many mechanisms of tumor immune escape, including immunosuppression, which has become a research hotspot in recent years. The programmed death ligand-1/programmed death-1 (PD-L1/PD-1) signaling pathway is an important component of tumor immunosuppression, which can inhibit the activation of T lymphocytes and enhance the immune tolerance of tumor cells, thereby achieving tumor immune escape. Therefore, targeting the PD-L1/PD-1 pathway is an attractive strategy for cancer treatment; however, the therapeutic effectiveness of PD-L1/PD-1 remains poor. This situation requires gaining a deeper understanding of the complex and varied molecular mechanisms and factors driving the expression and activation of the PD-L1/PD-1 signaling pathway. In this review, we summarize the regulation mechanisms of the PD-L1/PD-1 signaling pathway in the tumor microenvironment and their roles in mediating tumor escape. Overall, the evidence accumulated to date suggests that induction of PD-L1 by inflammatory factors in the tumor microenvironment may be one of the most important factors affecting the therapeutic efficiency of PD-L1/PD-1 blocking.
肿瘤免疫逃逸是肿瘤生存的重要策略。肿瘤免疫逃逸的机制有很多，其中免疫抑制是近年来的研究热点。程序性死亡配体 1/程序性死亡受体 1（PD-L1/PD-1）信号通路是肿瘤免疫抑制的重要组成部分，它可以抑制 T 淋巴细胞的激活，增强肿瘤细胞的免疫耐受，从而实现肿瘤免疫逃逸。因此，靶向 PD-L1/PD-1 通路是癌症治疗的一个有吸引力的策略；然而，PD-L1/PD-1 的治疗效果仍然很差。这种情况需要更深入地了解驱动 PD-L1/PD-1 信号通路表达和激活的复杂多样的分子机制和因素。在这篇综述中，我们总结了 PD-L1/PD-1 信号通路在肿瘤微环境中的调控机制及其在介导肿瘤逃逸中的作用。总的来说，迄今为止积累的证据表明，肿瘤微环境中炎症因子诱导的 PD-L1 可能是影响 PD-L1/PD-1 阻断治疗效率的最重要因素之一。
