Guo Yilin, Lu Jiaxue, Li Xiaoxu, Yan Shiqi, Zhou Jieyu, Tian Ziying, Liu Ying, Li Nan, Zhou Qing, Li Xiayu, Shi Lei, Jiang Su, Li Mengna, Zhou Xiao, Huang Donghai, Zeng Zhaoyang, Fan Songqing, Xiong Wei, Zhou Ming, Li Guiyuan, Zhang Wenling
Department of Medical Laboratory Science, the Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
Department of Blood Transfusion, Children's Hospital Affiliated to Zhengzhou University,Henan Children's Hospital, Zhengzhou Children's Hospital, Zhengzhou, Henan, China.
Int J Biol Sci. 2025 Feb 10;21(5):1914-1931. doi: 10.7150/ijbs.103703. eCollection 2025.
Therapeutic strategies aimed at harnessing anti-tumor immunity are being intensively investigated as they show promising results in cancer treatment. The PD-1/ PD-L1 pathway is an essential target for restoring functional anti-tumor immune response. BRD7 is a candidate tumor suppressor gene and nuclear transcription factor of nasopharyngeal carcinoma (NPC) which was cloned in our laboratory. In this paper, we reported that the candidate tumor suppressor gene BRD7 was strongly associated with good prognosis of NPC patients and negatively regulated PD-L1 expression. In addition, we found that BRD7 down-regulated PD-L1 expression and enhanced the killing function of CD8 T lymphocytes in NPC cells through binding to p85α via the 485-651 domain and inhibiting the activity of PI3K, thereby inhibiting the activity of PI3K/AKT/mTOR/STAT3 pathway. experiments, the results showed that BRD7 could not only inhibit the growth of tumors, but also play a better anti-tumor effect when combined with PD-L1 antibody. These results provided further evidence that BRD7 inhibited immune escape of NPC through down-regulating PD-L1 expression.
旨在利用抗肿瘤免疫的治疗策略正在深入研究中，因为它们在癌症治疗中显示出有前景的结果。PD-1/PD-L1通路是恢复功能性抗肿瘤免疫反应的关键靶点。BRD7是一种候选肿瘤抑制基因，也是本实验室克隆的鼻咽癌（NPC）核转录因子。在本文中，我们报道候选肿瘤抑制基因BRD7与NPC患者的良好预后密切相关，并负向调节PD-L1表达。此外，我们发现BRD7通过485-651结构域与p85α结合并抑制PI3K活性，从而下调PD-L1表达并增强NPC细胞中CD8 T淋巴细胞的杀伤功能，进而抑制PI3K/AKT/mTOR/STAT3通路的活性。实验结果表明，BRD7不仅能抑制肿瘤生长，而且与PD-L1抗体联合使用时具有更好的抗肿瘤效果。这些结果进一步证明BRD7通过下调PD-L1表达抑制NPC的免疫逃逸。
