Abstract
The interaction between cancer cells and immune cells is important for the cancer development. However, much attention has been given to T cells and macrophages. Being the most abundant leukocytes in the blood, the functions of neutrophils in cancer have been underdetermined. They have long been considered an “audience” in the development of cancer. However, emerging evidence indicate that neutrophils are a heterogeneous population with plasticity, and subpopulation of neutrophils (such as low density neutrophils, polymorphonuclear-myeloid-derived suppressor cells) are actively involved in cancer growth and metastasis. Here, we review the current understanding of the role of neutrophils in cancer development, with a specific focus on their pro-metastatic functions. We also discuss the potential and challenges of neutrophils as therapeutic targets. A better understanding the role of neutrophils in cancer will discover new mechanisms of metastasis and develop new immunotherapies by targeting neutrophils.
Highlights
Cancer is a leading cause of death worldwide, and metastasis accounts for the majority of cancer-related mortality
While Circulating Tumor Cells (CTCs) use various strategies to survive in the intravascular environment, their metastatic potential eventually depends on their ability to rapidly extravasate into the surrounding tissue
Neutrophils within clusters are highly migratory, in a confined manner mediated by neutrophils self-secreted IL-8 and tumor-derived CXC chemokine ligand (CXCL)-1. This induces significant neutrophil sequestration with arrested tumor cells, leading to the spatial localization of neutrophil-derived IL-8, and increasing the extravasation potential of nearby entrapped tumor cells through disruption of the endothelial barrier. These findings provide a basis for inhibiting the pro-extravasation effect of neutrophils to reduce metastasis
Summary
Much attention has been given to T cells and macrophages. Being the most abundant leukocytes in the blood, the functions of neutrophils in cancer have been underdetermined. They have long been considered an “audience” in the development of cancer. Emerging evidence indicate that neutrophils are a heterogeneous population with plasticity, and subpopulation of neutrophils (such as low density neutrophils, polymorphonuclear-myeloid-derived suppressor cells) are actively involved in cancer growth and metastasis. We review the current understanding of the role of neutrophils in cancer development, with a specific focus on their pro-metastatic functions. A better understanding the role of neutrophils in cancer will discover new mechanisms of metastasis and develop new immunotherapies by targeting neutrophils
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