The role of tumor associated neutrophils in cancer

Neutrophils play an established role in host defense and in killing invading microorganisms. As so, they are traditionally considered in the context of their anti-bacterial functions. It is becoming increasingly clear that tumor-associated neutrophils (TAN) play a major role in cancer biology, and especially in the tumor immune-microenvironment. Neutrophils, the major immune cell in the blood in humans, make up also a significant portion of the inflammatory cell infiltrate in many types of cancer. Like all other leukocytes, they move into tissues under the influence of specific chemokines, cytokines and cell adhesion molecules, most of them coming from the tumor microenvironment, being responsible for their recruitment into the tumor. We have found that TAN are a distinct population of neutrophils, differing markedly in their transcriptomic profile from both naïve neutrophils and the granulocytic fraction of myeloid-derived suppressor cells (G-MDSC). Furthermore, we recently found that neutrophils in the tumor develop to have a pro-tumorigenic phenotype during tumor progression. Studies have demonstrated specific examples of tumor-mediated signals (such as transforming growth factor-β [TGF-β]) that induce the formation of a pro-tumorigenic (N2) phenotype capable of supporting tumor growth and suppressing the anti-tumor immune response. Other studies show that TAN can also have an anti-tumorigenic (N1) phenotype. We explore here the literature on the different mechanisms of TAN-recruitment to tumors, the unique characteristics of TAN in animals and humans, and what shapes their pro- and/or anti-tumor effects.