This study investigates the role of purine metabolism (PM) in lung adenocarcinoma (LUAD) using single-cell analysis. The authors employed various scoring methods to assess PM activity across different cell types and identified epithelial and myeloid cells in the tumor microenvironment (TME) as having the highest PM scores. They found that high PM scores were associated with increased intercellular communication, particularly in fibroblasts, epithelial, myeloid, and endothelial cells. A robust purine metabolism-associated signature (PAS) was developed using PM-related genes, which demonstrated strong prognostic predictive capability. Patients with low PAS scores exhibited better prognoses and showed increased immune cell infiltration, elevated CD8A expression, and reduced PD-L1 expression. The PAS score also correlated with improved responses to immunotherapy across multiple datasets. The study highlights the potential of the PAS score as a valuable tool for selecting LUAD patients likely to benefit from future clinical stratification efforts and immunotherapy.This study investigates the role of purine metabolism (PM) in lung adenocarcinoma (LUAD) using single-cell analysis. The authors employed various scoring methods to assess PM activity across different cell types and identified epithelial and myeloid cells in the tumor microenvironment (TME) as having the highest PM scores. They found that high PM scores were associated with increased intercellular communication, particularly in fibroblasts, epithelial, myeloid, and endothelial cells. A robust purine metabolism-associated signature (PAS) was developed using PM-related genes, which demonstrated strong prognostic predictive capability. Patients with low PAS scores exhibited better prognoses and showed increased immune cell infiltration, elevated CD8A expression, and reduced PD-L1 expression. The PAS score also correlated with improved responses to immunotherapy across multiple datasets. The study highlights the potential of the PAS score as a valuable tool for selecting LUAD patients likely to benefit from future clinical stratification efforts and immunotherapy.