Disease-associated neutrophil heterogeneity in cancer therapy: Implications for precision immunotherapy

Neutrophils exhibit significant heterogeneity and functional plasticity in both healthy and disease states. Patients often suffer from multiple conditions simultaneously, complicating disease-associated neutrophil functions. This complexity challenges tumor-related research, yet current studies frequently overlook the functional differences of neutrophils across health and disease, which may contribute to unsatisfactory anti-tumor drug outcomes. This article reviews six conditions that affect neutrophil functions and influence tumor treatment efficacy: inflammation, aging, obesity, diabetes, thrombosis, and liver injury. It highlights how neutrophil phenotypes and functions change under these conditions, potentially altering their roles in tumor immunity and impacting anti-tumor therapies. Furthermore, four anti-tumor strategies targeting neutrophils are discussed, such as neutrophil drug delivery systems, neutrophil reprogramming, regulation of neutrophil extracellular traps, and the use of neutrophil membranes and exosomes. This review offers a novel perspective: for cancer patients with concurrent comorbidities (such as inflammation, aging, obesity, diabetes, thrombosis, and liver injury), tailoring treatment by targeting or leveraging neutrophils in these disease states may be of significant importance.