Neutrophil Maturity in Cancer

Abstract

Neutrophils are implicated in almost every stage of oncogenesis and paradoxically display anti- and pro-tumor properties. Accumulating evidence indicates that neutrophils display diversity in their phenotype resulting from functional plasticity and/or changes to granulopoiesis. In cancer, neutrophils at a range of maturation stages can be identified in the blood and tissues (i.e., outside of their developmental niche). The functional capacity of neutrophils at different states of maturation is poorly understood resulting from challenges in their isolation, identification, and investigation. Thus, the impact of neutrophil maturity on cancer progression and therapy remains enigmatic. In this review, we discuss the identification, prevalence, and function of immature and mature neutrophils in cancer and the potential impact of this on tumor progression and cancer therapy.

Keywords: cancer; cancer inflammation; granulopoiesis; myeloid; neutrophil.

Figure 1

Immature neutrophils are present in cancer and have an altered functional capacity compared to mature that may influence tumor progression. Immature neutrophils can be present and significantly increased in the peripheral blood and tissues of cancer patients. This increase may result from: (A) promotion of their early release from their bone marrow (BM) haematopoietic niche by increased systemic chemokines, such as granulocyte colony-stimulating (G-CSF), e.g., tumor produced or as therapy. (B) release of neutrophil precursors from the BM and their extramedullary proliferation in the circulation or tissues. Immature neutrophils may have both anti- and pro-tumor properties. These include (C) altered localization resulting from their differential cell surface marker expression influencing their chemotactic capacity and/or less segmented nuclear morphology compared to mature neutrophils reducing their deformability and (D) different functional capacity compared to mature neutrophils including their reduced phagocytic capacity, altered suppressive properties, reduced NETosis, and reduced granularity. (E) Together, these differences in the properties and functions of immature neutrophils could lead to their negative influence when targeting neutrophils in cancer therapy. G-CSF, colony stimulating factor-3; GMP, granulocyte monocyte progenitor; ROS, reactive oxygen species; NET, neutrophil extracellular trap; NK, natural killer cell.