Role of Neutrophils in Homeostasis and Diseases

Neutrophils, constituting a predominant subset of innate immune cells in mammalian systems, play pivotal roles in pathogenic clearance and homeostatic maintenance. In the progressive development of cancer, neutrophils exert dual roles in both anticancer and procancer processes through their heterogeneity. In recent years, research into the role of neutrophils in cancer and various nontumor diseases has been continuously deepening. However, current research in this area remains incomplete. This review comprehensively summarizes the tissue homing dynamics, lifespan regulation, and physiological functions of neutrophils, starting from their development and heterogeneity. Furthermore, we delineate the dual regulatory functions of neutrophils in carcinogenesis, encompassing both tumor-suppressive mechanisms and protumor mechanisms. This section further synthesizes recent advancements in neutrophil-targeted therapeutic platforms and biomimetic delivery systems, while critically evaluating persistent methodological and translational challenges in clinical applications. In addition, we systematically analyze the role of neutrophils in non-neoplastic diseases and list several typical diseases, including infectious diseases. Finally, we also discuss current controversies and research perspectives on neutrophils. It is hoped that this review will deepen insights into the role of neutrophils in homeostasis and disease, while exploring their potential in disease treatment.