Versatile neutrophil functions in cancer

Neutrophils have historically been considered a singular, terminally-differentiated cell population, replete with pre-formed granules, poised to react quickly, aggressively, and somewhat non-specifically in the face of a microbial challenge or tissue injury. However, in recent years, neutrophil biologists have started revisiting this simplistic conception. Many studies have identified complexities in neutrophil biology, and these findings have led the field to redefine neutrophil heterogeneity from multiple angles including their development and maturation, their tissue location, and their ability to respond to various (pathological) stimuli. In this review, we discuss the importance of this reassessment within the context of cancer. Experimental evidence supports that neutrophil behavior is diverse, context-dependent, and manipulable; cutting-edge technologies have enabled the identification of neutrophil heterogeneity with high resolution and in an unbiased manner, revealing what may be critical underpinnings of these diverse behaviors, and enabling sophisticated computational assessments of specific programs and interactions. We are coming ever closer to delineating a holistic picture of neutrophil heterogeneity and how it may interplay with cancer stage, tumor microenvironment, and therapy. All of this together paints a promising picture when considering how clinical practice may harness the heterogeneity of these cells, for biomarkers or therapeutic approaches, leveraging what we are learning about these powerful and plentiful immune effectors.