Potential of Adora2b as an immunotherapeutic target for gastric cancer
Jie Li1,2, Ruixin Shi1,2, Xinyao Zhang1,2
1Inner Mongolia Medical University Affiliated Cancer Hospital, Hohhot, China.
Abstract:
Gastric cancer (GC) is characterized by highly heterogeneous tumors, whose progression is genetically driven and closely associated with hypoxia and an immunosuppressive tumor microenvironment (TME). Hypoxia accelerates adenosine accumulation, activates the low-affinity Adora2b receptor, weakens antitumor immunity, and promotes metastasis. Adora2b is lowly expressed in normal gastric mucosa. Still, it is significantly upregulated in diseased tissues, where it is widely expressed in various immune cells and the tumor stroma, mediating immune escape, fibrosis, and vascular remodeling. This review summarizes the cell-type-specific signaling mechanisms of Adora2b in the TME (e.g., T cells, macrophages) and, drawing on research in other tumors, proposes mechanistic explanations for its tissue-specific roles. Based on existing evidence, Adora2b regulates epithelial-mesenchymal transition (EMT) in GC cells via the cAMP/PKA/Snail pathway, and preclinical studies show that targeting Adora2b reduces the migration and invasion of GC cells. These findings suggest that targeting Adora2b may provide new insights for gastric cancer therapy.
Insights
Targeting the Adora2b receptor in gastric cancer (GC) may offer a new therapeutic strategy. Blocking Adora2b can potentially reduce tumor cell migration and invasion, impacting cancer progression within the tumor microenvironment.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Gastric cancer (GC) presents as heterogeneous tumors influenced by genetic factors, hypoxia, and an immunosuppressive tumor microenvironment (TME).
- Hypoxia promotes adenosine accumulation, activating the Adora2b receptor, which impairs anti-tumor immunity and facilitates metastasis.
- Adora2b, upregulated in GC tissues, is expressed on immune cells and tumor stroma, contributing to immune evasion, fibrosis, and vascular remodeling.
Purpose of the Study:
- To review the cell-specific signaling mechanisms of Adora2b within the TME.
- To explore the tissue-specific functions of Adora2b by referencing research from other tumor types.
- To investigate Adora2b's role in GC progression, particularly epithelial-mesenchymal transition (EMT).
Main Methods:
- Literature review focusing on Adora2b signaling in the TME.
- Analysis of Adora2b expression patterns in normal versus diseased gastric tissues.
- Examination of Adora2b's downstream effects, including EMT regulation via the cAMP/PKA/Snail pathway.
Main Results:
- Adora2b is significantly upregulated in GC and expressed across various immune cells and stromal components.
- Adora2b signaling is implicated in immune escape, fibrosis, and vascular remodeling within the TME.
- Adora2b regulates EMT in GC cells through the cAMP/PKA/Snail pathway, influencing migration and invasion.
Conclusions:
- Targeting Adora2b presents a promising therapeutic avenue for gastric cancer.
- Inhibition of Adora2b has demonstrated potential in preclinical models to reduce GC cell migration and invasion.
- Understanding Adora2b's role offers new insights for developing novel gastric cancer treatments.
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