TNF and neoplasm: In CRC or melanoma models, Gln supplementation enhances CD8+ T cell abundance and effector functions (IFN-γ/TNF/granzyme B) (255), whereas pharmacological inhibition or genetic ablation of tumor Gln metabolism (e.g., glutaminase knockout) not only suppresses cancer growth but also alleviates microenvironmental hypoxia, acidosis, and nutrient exhaustion, thereby augmenting CD8+ T cell antitumor activity (Figure 4) (256).