Li Hong-Jiang, Yu Zhi-Yun, Gao Hua-Ping, Xu Yi-Ran, Li Xue-Yuan, Jiang Wei, Chen Di, Yan Dong-Ming, Yang Chao, Liu Xian-Zhi
Department of Neurosurgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Henan Key Laboratory of Child Brain Injury and Henan Clinical Research Center for Child Neurological Disorders, Institute of Neuroscience, Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Front Oncol. 2025 May 1;15:1545780. doi: 10.3389/fonc.2025.1545780. eCollection 2025.
Glioma, the primary cancerous tumor of the central nervous system in adults, has a poor outlook. Immune checkpoint blockade therapy has exhibited notable efficacy against various cancer types. Prior research has suggested that the adenosine A1 receptor (ADORA1) facilitates the proliferation of tumors in cancer. Nevertheless, the precise impact of ADORA1 on glioma progression and its influence on anti-programmed death receptor 1 (PD1) therapy, along with the underlying regulatory mechanisms, remain to be fully elucidated.
Bioinformatics was used to explore the correlation between ADORA1 expression and glioma prognosis. The effects of ADORA1 on glioma and anti-PD1 therapy were investigated in both laboratory settings and living organisms.
The results revealed a significant increase in ADORA1 expression in glioma, which was correlated with poor prognosis. Furthermore, ADORA1 inhibition facilitated glioma apoptosis by augmenting kininogen-1 (KNG1). ADORA1 inhibition enhanced T cell recruitment and increased glioma susceptibility to anti-PD1 therapy.
Our findings indicate that inhibiting ADORA1 can induce apoptosis in glioma cells and increase their sensitivity to anti-PD1 therapy. ADORA1 may serve as a prognostic marker for glioma and a potential target to enhance the effectiveness of anti-PD-1 therapy.
胶质瘤是成人中枢神经系统的原发性癌性肿瘤,预后较差。免疫检查点阻断疗法已显示出对多种癌症类型具有显著疗效。先前的研究表明,腺苷A1受体(ADORA1)促进癌症中肿瘤的增殖。然而,ADORA1对胶质瘤进展的确切影响及其对抗程序性死亡受体1(PD1)治疗的影响,以及潜在的调控机制,仍有待充分阐明。
利用生物信息学探索ADORA1表达与胶质瘤预后之间的相关性。在实验室环境和生物体中研究了ADORA1对胶质瘤和抗PD1治疗的影响。
结果显示胶质瘤中ADORA1表达显著增加,这与预后不良相关。此外,ADORA1抑制通过增强激肽原-1(KNG1)促进胶质瘤细胞凋亡。ADORA1抑制增强了T细胞募集,并增加了胶质瘤对抗PD1治疗的敏感性。
我们的研究结果表明,抑制ADORA1可诱导胶质瘤细胞凋亡,并增加其对抗PD1治疗的敏感性。ADORA1可能作为胶质瘤的预后标志物以及增强抗PD-1治疗效果的潜在靶点。