The heterogeneity of neutrophils in cancer and its implication for therapeutic targeting

Neutrophils have a pivotal role in safeguarding the host against pathogens and facilitating tissue remodeling. They possess a large array of tools essential for executing these functions. Neutrophils have a critical role in cancer, where they are largely associated with negative clinical outcome and resistance to therapy. However, the specific role of neutrophils in cancer is complex and controversial, owing to their high functional diversity and acute sensitivity to the microenvironment. In this Perspective, we discuss the accumulated evidence that suggests that the functional diversity of neutrophils can be ascribed to two principal functional states, each with distinct characteristics: classically activated neutrophils and pathologically activated immunosuppressive myeloid-derived suppressor cells. We discuss how the antimicrobial factors in neutrophils can contribute to tumor progression and the fundamental mechanisms that govern the pathologically activated myeloid-derived suppressor cells. These functional states play divergent roles in cancer and thus require separate consideration in therapeutic targeting. Gabrilovich and colleagues discuss how the functional diversity of neutrophils in cancer can be ascribed to two functional states: classically activated neutrophils and pathologically activated myeloid-derived suppressor cells.