Neutrophils at the Crossroads: Unraveling the Multifaceted Role in the Tumor Microenvironment

Abstract

Over the past decade, research has prominently established neutrophils as key contributors to the intricate landscape of tumor immune biology. As polymorphonuclear granulocytes within the innate immune system, neutrophils play a pivotal and abundant role, constituting approximately ∼70% of all peripheral leukocytes in humans and ∼10–20% in mice. This substantial presence positions them as the frontline defense against potential threats. Equipped with a diverse array of mechanisms, including reactive oxygen species (ROS) generation, degranulation, phagocytosis, and the formation of neutrophil extracellular traps (NETs), neutrophils undeniably serve as indispensable components of the innate immune system. While these innate functions enable neutrophils to interact with adaptive immune cells such as T, B, and NK cells, influencing their functions, they also engage in dynamic interactions with rapidly dividing tumor cells. Consequently, neutrophils are emerging as crucial regulators in both pro- and anti-tumor immunity. This comprehensive review delves into recent research to illuminate the multifaceted roles of neutrophils. It explores their diverse functions within the tumor microenvironment, shedding light on their heterogeneity and their impact on tumor recruitment, progression, and modulation. Additionally, the review underscores their potential anti-tumoral capabilities. Finally, it provides valuable insights into clinical therapies targeting neutrophils, presenting a promising approach to leveraging innate immunity for enhanced cancer treatment.

Exploiting tertiary lymphoid structures gene signature to evaluate tumor microenvironment infiltration and immunotherapy response in colorectal cancer

“…Studies by Qin F et al indicated that anti-TGF-b facilitates neutrophils recruitment and polarizes neutrophils towards an antitumor phenotype (N1) in CRC (39). Meanwhile, tumor infiltrating neutrophils can exert the role of antigen-presenting cells and heighten T cell proliferation (40). T FH cells are usually accompanied by high CXCR5, CD40, and CXCL13 expression.…”

Exploring osteosarcoma based on the tumour microenvironment

“…Based on the ndings from GO, KEGG, and GSEA enrichment analyses, numerous differentially expressed genes (DEGs) showed enrichment in pathways related to the immune system.Neutrophil chemotaxis was associated with more DEGs during BP in all GOs. Previous studies have shown that neutrophils are a major component of TME [17], which can exert a tumour-killing effect by affecting T cells [18,19]. In this study, two groups with high and low levels of immune activation were also studied in depth, and noticeable variances were observed in the extent of immune cell in ltration between the two groups, and the level of immune cell in ltration in the high-immunity group was signi cantly higher than that in the low-immunity group, which may be associated with the high survival rate of the high-immunity group.…”