Intratumoral pro-oxidants promote cancer immunotherapy by recruiting and reprogramming neutrophils to eliminate tumors

Neutrophils have recently gained recognition for their potential in the fight against cancer. Neutrophil plasticity between the N1 anti-tumor and N2 pro-tumor subtypes is now apparent, as is the ability to polarize these individual subtypes by interventions such as intratumoral injection of various agents including bacterial products or pro-oxidants. Metabolic responses and the production of reactive oxygen species (ROS) such as hydrogen peroxide act as potent chemoattractants and activators of N1 neutrophils that facilitates their recruitment and ensuing activation of a toxic respiratory burst in tumors. Greater understanding of the precise mechanism of N1 neutrophil activation, recruitment and regulation is now needed to fully exploit their anti-tumor potential against cancers both locally and at distant sites. This systematic review critically analyzes these new developments in cancer immunotherapy.