Target neutrophil heterogeneity and plasticity in cancer

Abstract

Neutrophils have long been regarded as cells of a limited lifespan, known to produce pro-inflammatory molecules, and primarily engaged in combating infections. However, recent advancements in single-cell analysis and molecular biology have revealed their remarkable heterogeneity and plasticity, particularly within the context of tumors. This review explores the development and diversity of neutrophils under both physiological and pathological conditions, with a particular focus on their roles in cancer. The discussion encompasses the emergence of distinct neutrophil subtypes, particularly senescent neutrophils, within tumors and their context-dependent functions in tumorigenesis, progression, metastasis, and recurrence. The plasticity of these cells, driven by intrinsic factors and the tumor microenvironment, allows them to be reprogrammed between pro-tumor and anti-tumor phenotypes. This process is influenced by cytokines, metabolic reprogramming, and interactions with other immune cells. The potential of targeting and engineering neutrophil as a therapeutic avenue for cancer treatment is further underscored, including the use of senolytic agents, metabolic inhibitors, and reprogramming strategies. Finally, future research directions are proposed to further elucidate the mechanisms underlying neutrophil heterogeneity and plasticity, with the aim of developing novel therapeutic approaches to modulate neutrophil function in cancer.