Nucleotide signaling in neutrophils: a key player in cancer dynamics

Neutrophils are key innate immune cells whose effector mechanisms are increasingly recognized as therapeutic targets in chronic inflammation and cancer. While highly heterogeneous and functionally versatile, they can also exacerbate inflammation and tissue damage, making precise modulation critical for homeostasis. Nucleotide signaling-including extracellular nucleotide-metabolizing enzymes and receptors for ATP, UTP, and adenosine-plays a central role in regulating neutrophil responses. Extracellular nucleotides influence adhesion, chemotaxis, and degranulation, with important implications in cancer. Neutrophil heterogeneity affects tumor progression through both pro- and antitumor mechanisms. This review summarizes these findings and highlights therapeutic strategies targeting nucleotide signaling to modulate neutrophil activity in cancer.