Neutrophils in the tumor microenvironment: trying to heal the wound that cannot heal

Abstract

Summary Neutrophils are the first responders to infection and injury and are critical for antimicrobial host defense. Through the generation of reactive oxidants, activation of granular constituents and neutrophil extracellular traps, neutrophils target microbes and prevent their dissemination. While these pathways are beneficial in the context of trauma and infection, their off-target effects in the context of tumor are variable. Tumor-derived factors have been shown to reprogram the marrow, skewing toward the expansion of myelopoiesis. This can result in stimulation of both neutrophilic leukocytosis and the release of immature granulocytic populations that accumulate in circulation and in the tumor microenvironment. While activated neutrophils have been shown to kill tumor cells, there is growing evidence for neutrophil activation driving tumor progression and metastasis through a number of pathways, including stimulation of thrombosis and angiogenesis, stromal remodeling, and impairment of T cell-dependent anti-tumor immunity. There is also growing appreciation of neutrophil heterogeneity in cancer, with distinct neutrophil populations promoting cancer control or progression. In addition to the effects of tumor on neutrophil responses, anti-neoplastic treatment, including surgery, chemotherapy, and growth factors, can influence neutrophil responses. Future directions for research are expected to result in more mechanistic knowledge of neutrophil biology in the tumor microenvironment that may be exploited as prognostic biomarkers and therapeutic targets.

Prognostic role of neutrophil‐to‐lymphocyte ratio in head and neck cancer: A meta‐analysis

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“…Second, immune cells can recognize and kill tumor cells. Tumor cells regulate the immune system around them and create an inflammatory microenvironment to facilitate tumor progression . Thus, the immune system plays a dual role in cancer progression.…”

Gut microbiota modulate host immune cells in cancer development and growth

“…Clinical studies in cancer patients statistically correlate high blood neutrophil numbers and especially a high neutrophil:lymphocyte ratio with poor clinical outcomes including shorter survival time and higher risk of metastases [43,44]. Likewise, neutrophils in the tumor micro-environment (tumor-associated neutrophils, TAN’s) have also been linked with poor neoplastic disease outcomes in the majority of studies, although with few exceptions [43–45].…”

Epidemiology and biology of relapse after stem cell transplantation

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