Tumor Associated Neutrophil Polarization and its Potential Effects in Cancer Therapy

Abstract

Neutrophils are the first line of defense against pathogens in the immune system, and also has important implications for the tumor micro-environment. The effect of neutrophils on cancer is a double-edged sword in that they can both promote or inhibit tumor growth. When in different tumor environments or exposed to different stimulation, neutrophils would polarize toward anti-tumorigenic N1 or pro-tumorigenic N2 phenotype. The exact mechanism to polarize N1 and N2 are not yet well understood, but it is currently known that IFN-β or stimulation of the pathogen-associated molecular patterns (PAMPs) pathway can cause N1 polarization. On the contrary, in the presence of TGF-β or IL-10, N2 polarization occurs. When N1 population is dominant in the tumor micro-environment, they will inhibit tumor growth and enhance the effect of immunotherapy. But vice versa, dominance of pro-tumorigenic N2 phenotype within the tumor would enhance inflammation leading to more aggressive tumor growth and also hinders the effect of immunotherapy. Therefore, it is very important to understand the subtype of tumor associated neutrophils in the tumor when determining appropriate cancer therapy.