Tumor-Mediated Neutrophil Polarization and Therapeutic Implications

Abstract

Neutrophils are immune cells with reported phenotypic and functional plasticity. Tumor-associated neutrophils display many roles during cancer progression. Several tumor microenvironment (TME)-derived factors orchestrate neutrophil release from the bone marrow, recruitment and functional polarization, while simultaneously neutrophils are active stimulators of the TME by secreting factors that affect immune interactions and subsequently tumor progression. Successful immunotherapies for many cancer types and stages depend on the targeting of tumor-infiltrating lymphocytes. Neutrophils impact the success of immunotherapies, such as immune checkpoint blockade therapies, by displaying lymphocyte suppressive properties. The identification and characterization of distinct neutrophil subpopulations or polarization states with pro- and antitumor phenotypes and the identification of the major TME-derived factors of neutrophil polarization would allow us to harness the full potential of neutrophils as complementary targets in anticancer precision therapies.

Keywords: immune cells; neutrophils; tumor microenvironment.

Figure 1

Neutrophils are recruited to the tumor site in response to TME-derived stimuli such as chemokines and cytokines (green arrows). Polarized TANs exert immunosuppressive and protumor functions with the aid of neutrophil-derived factors such as granule enzymes and reactive oxygen species (red arrows).