The following is a summary of “ADORA2B promotes proliferation and migration in head and neck squamous cell carcinoma and is associated with immune infiltration,” published in the April 2025 issue of the BMC Cancer by Li et al.

The adenosine A2B receptor (ADORA2B), a member of the G protein-coupled receptor family, has emerged as a crucial player in tumor biology and immune regulation across various malignancies. However, its function in head and neck squamous cell carcinoma (HNSC) remains largely uncharacterized. This study systematically investigates the expression profile, clinical relevance, immune modulatory effects, and therapeutic implications of ADORA2B in HNSC, integrating bioinformatics analyses with experimental validation.

TCGA and GEO were utilized to assess ADORA2B expression levels, their correlation with clinicopathological features, and prognostic impact in HNSC. Weighted gene co-expression network analysis (WGCNA) and gene enrichment analyses were performed to explore ADORA2B-associated signaling pathways. Tumor immune infiltration was evaluated using ESTIMATE and single-sample gene set enrichment analysis (ssGSEA). Sensitivity to immune checkpoint blockade (ICB) therapy and chemotherapeutic agents was examined using IMvigor210 and NCI-60 drug response datasets. Functional assays, including siRNA-mediated knockdown of ADORA2B, CCK-8 proliferation assay, colony formation, and wound healing assays, were conducted in vitro to confirm the biological role of ADORA2B in HNSC.

ADORA2B expression was markedly elevated in HNSC tumor samples relative to adjacent normal tissues. Elevated ADORA2B levels were significantly associated with advanced tumor stage and unfavorable survival outcomes, including decreased overall survival (OS) and progression-free survival (PFS). Functional enrichment analyses indicated that high ADORA2B expression was linked to the suppression of multiple immune-related signaling pathways. Tumors with elevated ADORA2B expression exhibited a distinctly immunosuppressive tumor microenvironment, reflected by reduced stromal and immune scores and diminished infiltration of immune effector cells. Moreover, high ADORA2B expression predicted inferior response rates to ICB therapy, suggesting a role in therapeutic resistance. Drug sensitivity profiling identified several compounds, such as Ixazomib citrate and Masitinib, as potentially effective in targeting tumors with elevated ADORA2B expression. In vitro experiments demonstrated that silencing ADORA2B significantly reduced HNSC cell proliferation, colony formation, and migration, reinforcing its role in tumor progression.

ADORA2B acts as a critical oncogene in HNSC, promoting tumor growth and contributing to immune evasion. Its overexpression is linked to poor clinical prognosis and reduced responsiveness to immunotherapy. These findings position ADORA2B as a promising biomarker for prognosis and treatment stratification, and as a potential therapeutic target to enhance outcomes in patients with HNSC.

Source: bmccancer.biomedcentral.com/articles/10.1186/s12885-025-14102-2