Promoting metastasis: neutrophils and T cells join forces

Abstract

The role neutrophils play in cancer is a matter of debate as both pro- and anti-tumor functions have been documented. In a recent publication in Nature, Coffelt et al. identify a new mechanism where neutrophils and T cells cooperate to generate metastasis-supporting immune suppression.

Figure 1

The consequences of the interplay between neutrophils and lymphocytes on tumor growth and metastatic progression. Neutrophils were previously shown to possess both tumor-promoting and tumor-limiting properties. Neutrophils have the capacity to propagate cytotoxic CD8⁺ cells, through secretion of factors such as TNFα, cathepsin G and neutrophil elastase, thereby limiting primary tumor growth. Coffelt et al. identified a tumor-promoting cascade where tumor-secreted IL-1β stimulates the secretion of IL-17α from γδ T cells. Consequently, neutrophils acquire a suppressive phenotype and inhibit the propagation of cytotoxic CD8⁺ cells, ultimately enhancing metastatic seeding in the pre-metastatic lung.