Neutrophils in the tumor microenvironment-foes or friends?

Neutrophils are the most abundant white blood cells in the human circulation and are usually associated with inflammation and with fighting infections. In recent years, the role of these cells during cancer progression has been a matter of increasing interest. Tumor-associated neutrophils (TANs) accumulate in cancer patients and represent an important negative prognostic marker in a broad variety of neoplasms. Accordingly, TANs represent a highly attractive therapeutic target. TAN may exhibit tumor-promoting or -inhibiting functions. Pro-tumor neutrophils support tumor angiogenesis and growth and promote metastatic dissemination of tumors via establishment of the premetastatic niche. Studies in animal models have already shown that the depletion of TANs or the inhibition of their migration bears therapeutic potential. Multiple pathways and mediators that induce pro-tumoral functions in neutrophils have been identified. In this review, we provide an up-to-date overview of the pro- and anti-tumor properties of neutrophils as well as the environmental cues that regulate these distinct functions. We also report on our own work that comprehensively investigated the role of neutrophils in head and neck cancer.