Neutrophil and Colorectal Cancer

Abstract

Colorectal cancer (CRC) is often associated with metastasis and recurrence and is the leading cause of cancer-related mortality. In the progression of CRC, recent studies have highlighted the critical role of neutrophils, particularly tumor-associated neutrophils (TANs). TANs have both tumor-promoting and tumor-suppressing activities, contributing to metastasis, immunosuppression, angiogenesis, and epithelial-to-mesenchymal transition. Tumor-promoting TANs promote tumor growth by releasing proteases, reactive oxygen species, and cytokines, whereas tumor-suppressing TANs enhance immune responses by activating T cells and natural killer cells. Understanding the mechanisms underlying TAN mobilization, plasticity, and their role in the tumor microenvironment has revealed potential therapeutic targets. This review provides a comprehensive overview of TAN biology in CRC and discusses both the tumor-promoting and tumor-suppressing functions of neutrophils. Novel therapeutic approaches targeting TANs, such as chemokine receptor antagonists, aim to modulate neutrophil reprogramming and offer promising avenues for improving treatment outcomes of CRC.

Keywords: cancer; chemokine; metastasis; tumor microenvironment; tumor-associated neutrophil.

Figure 1

Multiple functions of tumor-associated neutrophils (TANs). (A) Recruitment of TANs by tumor-derived chemokines. (B) Induction of genetic instability through ROS production and microRNAs (e.g., miR-23a, miR-155), leading to DNA damage. (C) Promotion of extracellular matrix (ECM) remodeling via degranulation and degradation involving MMPs, Bv8, and S100A8/A9, facilitating angiogenesis driven by VEGF. (D) Immunosuppression mediated by N2 TANs through interactions with T cells, NK cells, and T-reg cells, and polarization of macrophages into the M2 phenotype. Created with BioRender.com.