Neutrophils in the Tumor Microenvironment

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.

TrendsNeutrophils are recruited to wounds and sites of tissue damage by signals including hydrogen peroxide, chemokines, and cytokines, many of which also recruit neutrophils to the tumor microenvironment.Neutrophils reverse migrate from target tissues through interactions with macrophages and other cell types, thus contributing to resolution of inflammation.Tumor-associated neutrophils contribute to tumor progression, invasion, and angiogenesis; however, there is evidence that neutrophils can play both pro- and antitumor roles and that they may be polarized to either phenotype based on external cues.Targeting neutrophils through blockade of pro-recruitment signals or driving reverse migration of neutrophils from tumors to promote an anti-inflammatory environment could provide potential future therapeutic avenues in cancer.