Neutrophils in cancer-unresolved questions

There is growing recognition that neutrophils play an important role in cancer initiation, progression and metastasis. Although they are typically characterized as short-lived effector cells, neutrophils have been shown to acquire immunosuppressive and pro-tumorigenic functions that promote tumor progression and escape. As such, inhibition of their function or depletion of neutrophils are being explored as potential cancer therapies. However, growing evidence of neutrophil diversification in cancer and their potential anti-tumor roles raise many unresolved questions. Here, we review recent advances that address the definition, origin and function of neutrophils in cancer, and elaborate on obstacles that make the study of neutrophils challenging. We envision that this review will provide the groundwork for focused design of therapeutics that will specifically target "tumorreprogrammed" neutrophils while sparing normal neutrophils to improve patient outcomes.