Giese, Hind, and Huttenlocher review the complex, but incompletely understood neutrophil biology and function within the tumor microenvironment. Neutrophils can be pro-inflammatory or anti-inflammatory, and both of these subsets can exert direct and indirect pro-tumor or anti-tumor effects. Identification of surface markers that would distinguish between human neutrophils, tumor-associated neutrophils in different “polarization” states, and PMN-MDSCs presents a critical challenge to delineating specific neutrophil subtypes as well as describing the continuity and plasticity of neutrophil phenotypes within the TME.

Neutrophils act as the body's first line of defense against infection and respond to diverse inflammatory cues, including cancer. Neutrophils display plasticity with the ability to adapt their function in different inflammatory contexts. In the tumor microenvironment, neutrophils have varied functions and have been classified using different terms including N1/N2 neutrophil, tumor-associated neutrophil (TAN), and polymorphonuclear-myeloid derived suppressor cell (PMN-MDSC). These populations of neutrophils are primarily defined by their functional phenotype as few specific cell surface markers have been identified. In this review, we will discuss neutrophil polarization, plasticity, and the function of pro-inflammatory/anti-inflammatory and pro-tumor/anti-tumor neutrophils in the tumor microenvironment. We will also discuss how neutrophils with the ability to suppress T cell activation, referred to by some as "PMN-MDSCs", fit into this paradigm.

Author Info: (1) Department of Medical Microbiology and Immunology, University of Wisconsin-Madison, United States. (2) Department of Medical Microbiology and Immunology, University of Wisconsi

Author Info: (1) Department of Medical Microbiology and Immunology, University of Wisconsin-Madison, United States. (2) Department of Medical Microbiology and Immunology, University of Wisconsin-Madison, United States. (3) Department of Pediatrics, University of Wisconsin-Madison, United States huttenlocher@wisc.edu.