Abstract & Overview
Tumor Associated Neutrophils (TANs) are recruited to the tumor microenvironment by cytokines and chemokines, can be classified according to their activation and cytokine status and effects on tumor cell growth in N1 and N2 TANs. N1 TANs exert an antitumor activity, by direct or indirect cytotoxicity. On the other hand, N2 TANs promote immunosuppression, tumor growth, angiogenesis and metastasis by DNA instability, or by cytokines and chemokines release. In tumor patients, either a high number of TANs and Neutrophil-to-Lynphocyte Ratio (NLR) do correlate with poor prognosis, and, so far, TAN counts and NLR can be regarded as biomarkers. Due to the key role of TANs in promoting tumor progression, therapeutic strategies to target TANs have been suggested, and two major approaches have been proposed: a) targeting the CXCL-8/CXCR-1/CXCR-2 axis, thereby depleting TANs entirely or b) targeting specific polymorpho- nuclear cell derived substances that promote tumor growth. Many studies have been accomplished either in vitro and in animal models, whereas clinical studies are restrained, presently, due to the risk of inducing immunosuppression. In this review, we deeply discuss the anti-tumorigenic or pro-tumorigenic activity of TANs. In particular, TANs relevance in tumor prognosis and in vitro therapeutic strategies are widely described. On-going clinical trials, aimed to inhibit neutrophil recruitment into the tumor are also accurately debated.