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Review
. 2016 Jan;37(1):41-52.
doi: 10.1016/j.it.2015.11.008. Epub 2015 Dec 14.

Neutrophils in the Tumor Microenvironment

Davalyn R Powell  1 , Anna Huttenlocher  2
Affiliations
Review

Neutrophils in the Tumor Microenvironment

VSports手机版 - Davalyn R Powell et al. Trends Immunol. 2016 Jan.

Abstract

Neutrophils are the first responders to sites of acute tissue damage and infection. Recent studies suggest that in addition to neutrophil apoptosis, resolution of neutrophil inflammation at wounds can be mediated by reverse migration from tissues and transmigration back into the vasculature. In settings of chronic inflammation, neutrophils persist in tissues, and this persistence has been associated with cancer progression. However, the role of neutrophils in the tumor microenvironment remains controversial, with evidence for both pro- and anti-tumor roles. Here we review the mechanisms that regulate neutrophil recruitment and resolution at sites of tissue damage, with a specific focus on the tumor microenvironment. We discuss the current understanding as to how neutrophils alter the tumor microenvironment to support or hinder cancer progression, and in this context outline gaps in understanding and important areas of inquiry VSports手机版. .

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Figures

Figure 1
Figure 1. Neutrophils in the wound microenvironment
Neutrophils are recruited to areas of wounding and tissue damage via pro-inflammatory signals including DAMPs, hydrogen peroxide, lipid mediators, and chemokines (1). Neutrophils can further influence the innate immune response to wounding by recruiting additional neutrophils, as well as macrophages which in turn can phagocytose neutrophils or drive reverse migration (2). In addition, neutrophils influence the wound healing by releasing factors including MMP9 and myeloperoxidase (3). Reverse migration of neutrophils is mediated by Redox signaling and LTB4-NE signaling which promotes reverse transendothelial migration back into the blood stream (4).
Figure 2
Figure 2. TAN interaction with the tumor microenvironment
Neutrophils are recruited to tumor sites via signals produced by cells of the tumor and microenvironment, including chemokines, cytokines, and hydrogen peroxide (1). These and other signals induce TANs to release factors which can remodel the ECM in the tumor microenvironment or act directly on tumor cells themselves to enhance tumor proliferation and invasion (2). In addition, some of these TAN-produced factors stimulate angiogenesis to support tumor growth and metastasis (3). Further evidence suggests that TANs interact with other immune cells such as CD8+ T cells. Depending on their polarity, TANs can have an immunosuppressive or immunostimulatory effects (4). While the TANs represented here are likely of the N2 pro-tumoral phenotype, the role of N1 neutrophils in targeting cancer cells and the N1/N2 polarization of neutrophils in response to cancer is an area of significant interest (5). Understanding how neutrophils are recruited and the complex ways they interact with cells within the tumor microenvironment will be important for the development of new therapies to treat cancer.
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References

    1. Kruger P, et al. Neutrophils: Between host defence, immune modulation, and tissue injury. PLoS Pathog. 2015;11:e1004651. - PMC - PubMed
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    1. Kolaczkowska E, Kubes P. Neutrophil recruitment and function in health and inflammation. Nature reviews. Immunology. 2013;13:159–175. - PubMed
    1. Pillay J, et al. In vivo labeling with 2H2O reveals a human neutrophil lifespan of 5.4 days. Blood. 2010;116:625–627. - PubMed
    1. Lakshman R, Finn A. Neutrophil disorders and their management. Journal of clinical pathology. 2001;54:7–19. - V体育ios版 - PMC - PubMed

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