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Polymorphonuclear Neutrophils and Tumors: Friend or Foe?

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Interaction of Immune and Cancer Cells

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Abstract

The tumor microenvironment is a dynamic network which apart from cancer cells includes also cells of the immune system such as polymorphonuclear neutrophils. Neutrophils are implicated in the interaction with cancer cells and, due to their ability of secreting the variety of active proteins and factors, play an important role in tumor progression and/or tumor destruction. In the tumor environment, neutrophils exist as anti-tumor phenotype (N1) and pro-tumoral phenotype (N2), analogous to the polarization of tumor-associated macrophages. The N1 phenotype of neutrophils is characterized by a cytotoxic and pro-inflammatory activity, while the N2 phenotype of cells has strong immunosuppressive properties. During cancer progression and metastasis, neutrophils facilitate and intensify extravasation of tumor cells as a result of the release of neutrophil metalloproteinases and elastase, which destroy the components of extracellular matrix, thus helping tumor cells to go through the endothelial barrier. On the other hand, tumor cells have a strong impact on the functional activity of neutrophils, and by causing immune system suppression in the host organism they promote the progression of the cancer. This review summarizes the pro- and anti-tumoral activity of neutrophils as the result of their direct contact with cancer cells and the release of different active mediators.

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Abbreviations

BMs:

Basement membranes

ECM:

Extracellular matrix

G-CSF:

Granulocyte colony-stimulating factor

GM-CSF:

Granulocyte–macrophage colony-stimulating factor

huGCP-2:

Human granulocyte chemotactic protein 2

ICAM-1:

Intracellular adhesion molecule 1

IFN:

Interferon

IL:

Interleukin

IRAK 1:

Interleukin-1 receptor-associated kinase 1

IRS-1:

Insulin receptor substrate-1

MIP-1 α:

Macrophage inflammatory protein-1 α

MMP:

Metalloproteinase

NE:

Neutrophil elastase

NK:

Natural killer

NN:

Naive neutrophils

PI3K:

Phosphatidylinositol-3 kinase

ROS:

Reactive oxygen species

TAMs:

Tumor-associated macrophages

TANs:

Tumor-associated neutrophils

TGF-β:

Transforming growth factor β

TLRs:

Toll-like receptors

TNF-α:

Tumor necrosis factor-α

TRAIL:

TNF-related apoptosis-inducing ligand

VCAM-1:

Vascular cell adhesion molecule-1

VEGF:

Vascular endothelial growth factor

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Acknowledgements

These research were supported in part by Grant NN 407095840 from National Science Center of Poland.

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  1. Institute of Medical Biology, Polish Academy of Sciences, Lodowa 106 str, 93-232, Lodz, Poland

    Magdalena Klink & Zofia Sulowska

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  1. Zofia Sulowska
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Correspondence to Magdalena Klink .

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  1. Institute of Medical Biology Polish Academy of Sciences, Lodz, Poland

    Magdalena Klink

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Klink, M., Sulowska, Z. (2014). Polymorphonuclear Neutrophils and Tumors: Friend or Foe?. In: Klink, M. (eds) Interaction of Immune and Cancer Cells. Springer, Vienna. https://doi.org/10.1007/978-3-7091-1300-4_7

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