血管生成素ANGPT2介导PD-L1上调在鼻咽癌免疫抑制中的作用及机制研究

Immune suppression microenvironment is an important reason of inducing anti-cancer therapy (including antiangiogenic therapy) failure in nasopharyngeal carcinoma (NPC). Recently it is reported that up-regulated ANGPT2 induce immune suppression, but mechanism is unknown. In preliminary study we found that ANGPT2 up-regulated PD-L1 after antiangiogenic therapy failure in NPC. Moreover we found that increased NF-κB may be involved in this mechanism. We make a scientific hypothesis that, ANGPT2 up-regulates PD-L1 via NF-κB pathway to induce immune suppression, finally results in the failure of anticancer therapy in NPC. This project could define the mechanism and role of ANGPT2 in the immune suppression of NPC, in order to provide experimental evidence and theoretical basis for the combination of antiangiogenic therapy and immunotherapy.

鼻咽癌免疫抑制微环境的形成是造成抗肿瘤治疗（包括抗血管生成治疗）失败的重要原因。近期研究报道血管生成素（ANGPT2）上调可导致免疫抑制微环境的产生，但具体机制不明。我们的预实验首次发现在鼻咽癌抗血管生成治疗失败后ANGPT2上调程序性死亡配体1（PD-L1），进一步预实验发现该过程伴随NF-κB上调。因此我们提出假设，鼻咽癌中ANGPT2通过NF-κB通路调控PD-L1导致免疫抑制微环境，从而导致鼻咽癌出现治疗耐药。本课题将通过研究ANGPT2调控PD-L1的机制，以及它们在鼻咽癌免疫抑制微环境中的作用，为鼻咽癌抗血管及免疫治疗联用提供实验证据和理论基础。