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Review
. 2019 Nov 15:9:1146.
doi: 10.3389/fonc.2019.01146. eCollection 2019.

Tumor Associated Neutrophils. Their Role in Tumorigenesis, Metastasis, Prognosis and Therapy

Maria Teresa Masucci  1 , Michele Minopoli  1 , Maria Vincenza Carriero  1
Affiliations
Review

Tumor Associated Neutrophils. Their Role in Tumorigenesis, Metastasis, Prognosis and Therapy

Maria Teresa Masucci et al. Front Oncol. .

Abstract

Tumor Associated Neutrophils (TANs) are engaged into the tumor microenvironment by cytokines and chemokines, can be distinguished according to their activation and cytokine status and effects on tumor cell growing in N1 and N2 TANs. N1 TANs exert an antitumor activity, by direct or indirect cytotoxicity. N2 TANs stimulate 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-Lymphocyte Ratio (NLR) do correlate with poor prognosis, and, so far, TAN counts and NLR can be regarded as biomarkers. Owing to the pivotal role of TANs in stimulating 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 blocking TANs or (b) targeting substances produced by polymorpho-nuclear cells 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.

Keywords: angiogenesis; neutrophil-to-lymphocyte ratio; tumor associated neutrophils; tumor microenvironment; tumorigenesis.

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Figures

Figure 1
Figure 1
Soluble factors promoting neutrophil recruitment into the tumor.
Figure 2
Figure 2
Neutrophils in bone marrow and circulation.
Figure 3
Figure 3
N1 and N2 TAN polarization and their activity.
Figure 4
Figure 4
Pro-tumor and anti-tumor functions of polarized neutrophils.
Figure 5
Figure 5
Therapeutic strategies for cancer neutrophils targeting.
See this image and copyright information in PMC

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