Neutrophils in Cancer: Molecular Mechanisms and Clinical Implications

Dear Colleagues,

Inflammation contributes to cancer progression by generating a pro-tumorigenic microenvironment containing numerous immune cells, which further activates other cancer hallmarks. Among these recruited immune cells, neutrophils are recognized as significant contributors to the promotion of cancer progression in multiple stages. Neutrophils, also known as polymorphonuclear granulocytes, are the largest subpopulation of leukocytes found in the blood. They are often considered the "first responder" immune cells owing to their rapidly recruitment to sites upon pathogen infection. The neutrophils' ability to eradicate pathogens was first attributed to their ability to directly phagocytose the pathogens or to expel the contents of their lytic, cytoplasmic granules into the extracellular space. However, in 2004, Brinkmann et al. discovered previously overlooked defense mechanisms which they named neutrophil extracellular traps (NETs), showing that neutrophils can extrude their chromatin into the extracellular space. Although NETs' function was initially related to pathogen killing, it quickly became apparent that the excess presence of NETs is negatively associated with many diseases, including cancer.

Given the significance of neutrophils in tumor cell proliferation, adhesion, distant metastasis, as well as tumor immunology, tumor-associated thrombosis, and other diseases, targeting neutrophils has the potential to generate therapeutic effects in treating cancer and other diseases. In order to better target neutrophils in cancer, it is important to identify the molecular pathways of neutrophil activation in different cancers. The next problem of concern is whether there are any synergistic or antagonistic effects between neutrophils and other immune cells. This is especially relevant after chemotherapy and immunotherapy as these are processes in which many immune cells can be reprogrammed or activated. It is important to avoid neutropenia when targeting neutrophils in cancer patients if neutrophils are antagonistic to therapies because neutrophils are critical to fighting off infections. Equally, it is important to avoid neutrophilia if the neutrophils are synergistic with therapies to prevent excessive tissue damage. Therefore, future studies must investigate the role of neutrophils combined with other therapies in cancer patients and determine the right balance to strike when targeting them. This will generate invaluable clinical data that will hopefully translate into clinical trials for use on cancer patients.

This Special Issue aims to provide insights into the potential roles of neutrophils in cancer and the clinical implications of potential therapeutic targeting of neutrophils. The editors cordially invite authors and investigators to submit original research, communications or review articles pertaining to the topic of this Issue.

Dr. Xue-Yan He
Guest Editor

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• neutrophil diversity
• neutrophil in homeostasis
• neutrophil extracellular traps (NETs) in cancer
• neutrophil proteases in cancer progression
• innate immune microenvironment in cancer
• neutrophil and metastases
• biomarkers
• targeting neutrophil in cancer
• neutrophil and cancer-related thrombosis
• cancer and the neutrophil life cycle