# Inhibiting ADORA1 enhances glioma apoptosis and increases its sensitivity to anti-PD1 therapy

**Authors:** Hong-jiang Li, Zhi-yun Yu, Hua-ping Gao, Yi-ran Xu, Xue-yuan Li, Wei Jiang, Di Chen, Dong-ming Yan, Chao Yang, Xian-zhi Liu

PMC · DOI: 10.3389/fonc.2025.1545780 · Frontiers in Oncology · 2025-05-01

## TL;DR

Inhibiting ADORA1 can increase glioma cell death and improve response to anti-PD1 therapy, offering a potential new treatment strategy.

## Contribution

This study reveals ADORA1 as a novel target to enhance glioma apoptosis and anti-PD1 therapy effectiveness.

## Key findings

- ADORA1 inhibition promotes glioma apoptosis via increased kininogen-1 (KNG1).
- ADORA1 inhibition enhances T cell recruitment and glioma sensitivity to anti-PD1 therapy.
- High ADORA1 expression correlates with poor glioma prognosis.

## Abstract

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.

## Linked entities

- **Genes:** ADORA1 (adenosine A1 receptor) [NCBI Gene 134], KNG1 (kininogen 1) [NCBI Gene 3827]
- **Diseases:** glioma (MONDO:0021042)

## Full-text entities

- **Genes:** Ctla4 (cytotoxic T-lymphocyte-associated protein 4) [NCBI Gene 12477] {aka Cd152, Ctla-4, Ly-56}, CD274 (CD274 molecule) [NCBI Gene 29126] {aka ADMIO5, B7-H, B7H1, PD-L1, PDCD1L1, PDCD1LG1}, Cd4 (CD4 antigen) [NCBI Gene 12504] {aka L3T4, Ly-4}, Klk1b9 (kallikrein 1-related peptidase b9) [NCBI Gene 13648] {aka EGF-BP C, Egfbp-3, Egfbp3, KAL, Klk9, kallikrein}, P9Ehs1 (protein, Chr 9, NIEHS 1) [NCBI Gene 109957], IDH1 (isocitrate dehydrogenase (NADP(+)) 1) [NCBI Gene 3417] {aka HEL-216, HEL-S-26, IDCD, IDH, IDP, IDPC}, Casp3 (caspase 3) [NCBI Gene 12367] {aka A830040C14Rik, AC-3, CASP-3, CC3, CPP-32, CPP32}, SOX2 (SRY-box transcription factor 2) [NCBI Gene 6657] {aka ANOP3, MCOPS3}, Pdcd1 (programmed cell death 1) [NCBI Gene 18566] {aka Ly101, PD-1, Pdc1}, KNG1 (kininogen 1) [NCBI Gene 3827] {aka BDK, BK, HAE6, HK, HMWK, KNG}, Pecam1 (platelet/endothelial cell adhesion molecule 1) [NCBI Gene 18613] {aka Cd31, PECAM-1, Pecam}, Kng1 (kininogen 1) [NCBI Gene 16644] {aka Kng}, Cd274 (CD274 antigen) [NCBI Gene 60533] {aka A530045L16Rik, B7h1, Pdcd1l1, Pdcd1lg1, Pdl1}, Gapdh (glyceraldehyde-3-phosphate dehydrogenase) [NCBI Gene 14433] {aka Gapd}, Lag3 (lymphocyte-activation gene 3) [NCBI Gene 16768] {aka CD223, LAG-3, Ly66}, CTLA4 (cytotoxic T-lymphocyte associated protein 4) [NCBI Gene 1493] {aka ALPS5, CD, CD152, CELIAC3, CTLA-4, GRD4}, CASP3 (caspase 3) [NCBI Gene 836] {aka CPP32, CPP32B, SCA-1}, Adora1 (adenosine A1 receptor) [NCBI Gene 11539] {aka A1-AR, A1AR, A1R, AA1R, ARA1, Ri}, Pik3r1 (phosphoinositide-3-kinase regulatory subunit 1) [NCBI Gene 18708] {aka PI3K, p50alpha, p55alpha, p85alpha}, IFNG (interferon gamma) [NCBI Gene 3458] {aka IFG, IFI, IMD69}, Ifng (interferon gamma) [NCBI Gene 15978] {aka IFN-g, If2f, Ifg}, PDCD1 (programmed cell death 1) [NCBI Gene 5133] {aka ADMIO4, AIMTBS, CD279, PD-1, PD1, SLEB2}, IL17A (interleukin 17A) [NCBI Gene 3605] {aka CTLA-8, CTLA8, IL-17, IL-17A, IL17, ILA17}, ADORA1 (adenosine A1 receptor) [NCBI Gene 134] {aka RDC7}, Akt1 (Akt serine/threonine kinase 1) [NCBI Gene 11651] {aka Akt, LTR-akt, PKB, PKB/Akt, PKBalpha, Rac}, Il17a (interleukin 17A) [NCBI Gene 16171] {aka Ctla-8, Ctla8, IL-17, IL-17A, Il17}, Mki67 (antigen identified by monoclonal antibody Ki 67) [NCBI Gene 17345] {aka D630048A14Rik, Ki-67, Ki67}
- **Diseases:** anaplastic astrocytoma (MESH:D001254), lung cancer (MESH:D008175), Anaplastic oligodendro (MESH:D002277), renal cancer (MESH:D007680), GBM (MESH:D005910), breast carcinoma (MESH:D001943), glioblastoma (MESH:D005909), X-YL (MESH:D000326), inflammation (MESH:D007249), brain tumors (MESH:D001932), oligodendroglioma (MESH:D009837), Cancer (MESH:D009369), hepatocellular carcinoma (MESH:D006528), melanoma (MESH:D008545)
- **Chemicals:** hematoxylin (MESH:D006416), DMEM (-), SDS (MESH:D012967), Paraformaldehyde (MESH:C003043), Triton X-100 (MESH:D017830), Alexa Fluor 555 (MESH:C000608607), crystal violet (MESH:D005840), sucrose (MESH:D013395), 4',6-diamidino-2-phenylindole (MESH:C007293), DAB (MESH:C000469), adenosine (MESH:D000241), isoflurane (MESH:D007530)
- **Species:** Homo sapiens (human, species) [taxon 9606], Mus musculus (house mouse, species) [taxon 10090]
- **Cell lines:** X-ZL — Homo sapiens (Human), Pleural biphasic mesothelioma, Cancer cell line (CVCL_5907), U87 — Homo sapiens (Human), Glioblastoma, Cancer cell line (CVCL_0022), GBM-Z1 — Homo sapiens (Human), Glioblastoma, Cancer cell line (CVCL_DG57), GL261 — Mus musculus (Mouse), Mouse glioblastoma, Cancer cell line (CVCL_Y003), C57BL/6N — Mus musculus (Mouse), Embryonic stem cell (CVCL_2H81)

## Full text

_Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC12078947/full.md

## Figures

8 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12078947/full.md

## References

30 references — full list in the complete paper: https://tomesphere.com/paper/PMC12078947/full.md

---
Source: https://tomesphere.com/paper/PMC12078947