Activated neutrophils: A next generation cellular immunotherapy

Cell therapies are at the forefront of novel therapeutics. Neutrophils, despite being the most populous immune cells in human blood circulation, are not considered a viable option for cellular therapies because of their short lifespan and poor understanding of their role in the pathophysiology of various diseases. In inflammatory conditions, neutrophils exhibit an activated phenotype. Activation brings about significant changes to neutrophil biology such as increased lifespan, inflammatory cytokine secretion, and enhanced effector functions. Activated neutrophils also possess the potential to stimulate the downstream immune response and are described as essential effectors in the immune response to tumors. This makes activated neutrophils an interesting candidate for cell therapies. Here, we review the biology of activated neutrophils in detail. We discuss the different ways neutrophils can be activated and the effect they have on other immune cells for stimulation of downstream immune response. We review the conditions where activated neutrophil therapy can be therapeutically beneficial and discuss the challenges associated with their eventual translation. Overall, this review summarizes the current state of understanding of neutrophil‐based immunotherapies and their clinical potential.