Physiological, patho-physiological, and potential therapeutic roles for neutrophils in cancer & beyond

Neutrophils are the most common type of white blood cell in the body, acting as crucial mediators of innate immunity. They initiate immune responses against invading microorganisms and threats like cancerous cells. Neutrophil infiltration is observed across inflammatory and autoimmune diseases and many cancers. Neutrophils orchestrate innate and adaptive immune responses to return the body to homeostasis, including after infections and preventing the development of tumours. While both protective and deleterious functions of neutrophils have been reported, this dual functionality reflects the heterogeneity of neutrophil subsets. Previously, neutrophils short lifespan resulted in their underappreciation. Recent advances in technology and methodology have drastically increased understanding of neutrophil biology, heterogeneity and plasticity, leading to a plethora of discoveries around the therapeutic potential of neutrophils, both through their direct cytotoxic effects to remove deleterious populations and through their ability to modulate other components of immunity. How to achieve this therapeutically with a rapidly-turned over population has proven elusive until now. This review highlights physiological and patho-physiological activities of neutrophil populations and their therapeutic potential and challenges. Recent and ongoing efforts to target or exploit neutrophil-type populations therapeutically have included engager-type antibody-based reagents and ‘off-the-shelf’ allogeneic cell therapy with and ‘Immuno-Modulatory Alpha Neutrophils’ (IMANs).