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Inhibiting ADORA1 enhances glioma apoptosis and increases its sensitivity to anti-PD1 therapy
Hong-Jiang Li1, Zhi-Yun Yu1, Hua-Ping Gao1
1Department of Neurosurgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Introduction:
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.
Methods:
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.
Results:
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.
Dicussion:
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.
Insights
Inhibiting the adenosine A1 receptor (ADORA1) in glioma promotes cancer cell death and enhances anti-programmed death receptor 1 (PD1) therapy effectiveness. ADORA1 is a potential prognostic marker for glioma.
Area of Science:
- Neuro-oncology
- Immunotherapy
- Molecular biology
Background:
- Glioma, a primary adult central nervous system tumor, has a poor prognosis.
- Adenosine A1 receptor (ADORA1) is implicated in tumor proliferation.
- The role of ADORA1 in glioma and its impact on anti-PD1 therapy are not fully understood.
Purpose of the Study:
- To investigate the role of ADORA1 in glioma progression.
- To determine the effect of ADORA1 on anti-PD1 therapy efficacy.
- To elucidate the regulatory mechanisms of ADORA1 in glioma.
Main Methods:
- Bioinformatic analysis of ADORA1 expression and glioma prognosis.
- In vitro and in vivo experiments to study ADORA1's effects on glioma.
- Assessment of ADORA1 inhibition's impact on apoptosis and immune cell infiltration.
Main Results:
- Elevated ADORA1 expression in glioma correlates with poor prognosis.
- ADORA1 inhibition induces glioma apoptosis via kininogen-1 (KNG1) augmentation.
- ADORA1 inhibition enhances T cell recruitment and improves response to anti-PD1 therapy.
Conclusions:
- ADORA1 inhibition triggers glioma cell apoptosis and sensitizes tumors to anti-PD1 therapy.
- ADORA1 serves as a potential prognostic biomarker for glioma.
- Targeting ADORA1 may enhance the efficacy of anti-PD1 immunotherapy for glioma patients.
