Neutrophil plasticity in the tumor microenvironment

Abstract

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 neutrophils, tumor-associated neutrophils, and polymorphonuclear neutrophil myeloid-derived suppressor cells (PMN-MDSCs). These populations of neutrophils are primarily defined by their functional phenotype, because few specific cell surface markers have been identified. In this review, we will discuss neutrophil polarization and plasticity and the function of proinflammatory/anti-inflammatory and protumor/antitumor 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.

Figure 1.

Neutrophils in the tumor microenvironment. Neutrophils can either promote or inhibit tumor growth depending on their polarization states. Antitumor neutrophils can directly kill tumor cells through release of reactive oxygen species (ROS) and reactive nitrogen species (RNS). They can also promote T-cell activation and recruit proinflammatory (M1) macrophages. In contrast, protumor neutrophils can release matrix metalloproteinase 9 (MMP9), which promotes angiogenesis and dissemination of tumor cells. They can also suppress natural killer (NK) cell function. Furthermore, they can recruit anti-inflammatory (M2) macrophages and T-regulatory cells. Finally, suppressor neutrophils, often referred to as polymorphonuclear neutrophil myeloid-derived suppressor cells (PMN-MDSCs), as well as other protumor neutrophils, can suppress CD8 T-cell function.