Neutrophils in cancer carcinogenesis and metastasis

Abstract

In recent years, neutrophils have attracted increasing attention because of their cancer-promoting effects. An elevated neutrophil-to-lymphocyte ratio is considered a prognostic indicator for patients with cancer. Neutrophils are no longer regarded as innate immune cells with a single function, let alone bystanders in the pathological process of cancer. Their diversity and plasticity are being increasingly recognized. This review summarizes previous studies assessing the roles and mechanisms of neutrophils in cancer initiation, progression, metastasis and relapse. Although the findings are controversial, the fact that neutrophils play a dual role in promoting and suppressing cancer is undeniable. The plasticity of neutrophils allows them to adapt to different cancer microenvironments and exert different effects on cancer. Given the findings from our own research, we propose a reasonable hypothesis that neutrophils may be reprogrammed into a cancer-promoting state in the cancer microenvironment. This new perspective indicates that neutrophil reprogramming in the course of cancer treatment is a problem worthy of attention. Preventing or reversing the reprogramming of neutrophils may be a potential strategy for adjuvant cancer therapy.

Cell Type-Specific Transcriptome Profiling Reveals a Role for Thioredoxin During Tumor Initiation

“…Neutrophils can produce proliferative factors such as IL-8 to directly promote tumor growth ( 11 ). It has been postulated that they can also release growth factors such as EGF, HGF, and PDGF ( 25 ).…”

The Good, the Bad, and the Ugly: Neutrophils, Angiogenesis, and Cancer

“…Similar to tumor-associated macrophages (TAMs), the phenotype and activity of TANs show significant heterogeneity throughout cancer development [75][76][77][78][79]. At the early stage of cancer, neutrophils are mainly located at the periphery of the tumor and display anti-tumoral phenotype, while, at later stages of the disease, their pro-tumoral properties dominate and support further cancer progression [57,[80][81][82][83][84][85]. The pro-or anti-tumoral phenotype of neutrophils in the primary tumor or metastatic site is highly dependent on the cytokine milieu [86].…”

CXCR2 Mediates Distinct Neutrophil Behavior in Brain Metastatic Breast Tumor

“…There is an increasing recognition of the diversity in neutrophils' functionalities and their plasticity within the pathology of tumors. Emerging evidence indicates that different subpopulations of neutrophils such as low-density neutrophils [75] or the polymorphonuclearmyeloid-derived suppressor cells resembling the neutrophils [76] are actively involved in cancer growth and metastasis [75][76][77][78]. Given that the plasticity of neutrophils enables them to adapt to different cancer microenvironments and exert different effects on cancer development, delineating the neutrophil heterogeneity and its interplay within the TIME could enable the discovery of new mechanisms of metastasis and help develop suitable immunotherapeutics by targeting neutrophils and their specific subtypes [77][78][79][80].…”

“…Emerging evidence indicates that different subpopulations of neutrophils such as low-density neutrophils [75] or the polymorphonuclearmyeloid-derived suppressor cells resembling the neutrophils [76] are actively involved in cancer growth and metastasis [75][76][77][78]. Given that the plasticity of neutrophils enables them to adapt to different cancer microenvironments and exert different effects on cancer development, delineating the neutrophil heterogeneity and its interplay within the TIME could enable the discovery of new mechanisms of metastasis and help develop suitable immunotherapeutics by targeting neutrophils and their specific subtypes [77][78][79][80]. The purpose of this study was to demonstrate how the mechanistic functionalities of a homogeneous population of neutrophils could dynamically acquire heterogeneity within a TIME, based on the metastatic potential of the tumor cells.…”