Metabolic Plasticity of Neutrophils: Relevance to Pathogen Responses and Cancer

Trends Cancer. 2021 Aug;7(8):700-713. doi: 10.1016/j.trecan.2021.04.007. Epub 2021 May 19.

Abstract

Neutrophils, the most abundant leukocyte population in humans, constantly patrol the body for foreign cells, including pathogens and cancer cells. Once neutrophils are activated, they engage distinct metabolic pathways to fulfill their specialized antipathogen functions. In this review, we examine current research on the metabolism of neutrophil differentiation and antipathogen responses. We also discuss how tumor-associated neutrophils (TANs) can be educated by cytokines and by the nutrient-restrictive milieu of the tumor microenvironment (TME) to suppress antitumor immunity, promote cancer progression, and contribute to biological heterogeneity among tumors. Last, we discuss the clinical implications of circulating neutrophils and infiltrating TANs and consider how targeting TAN metabolism may synergize with cancer immunotherapy.

Keywords: immunotherapy; metabolism; metastasis; neutrophils; tumor microenvironment.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Carcinogenesis / immunology
  • Carcinogenesis / pathology
  • Cytokines / immunology
  • Cytokines / metabolism
  • Glycolysis / immunology
  • Host-Pathogen Interactions / immunology*
  • Humans
  • Immunotherapy / methods*
  • Inflammation / immunology
  • Inflammation / metabolism
  • Inflammation / microbiology
  • Inflammation / therapy
  • Neoplasms / immunology*
  • Neoplasms / metabolism
  • Neoplasms / microbiology
  • Neoplasms / therapy
  • Neutrophils / immunology*
  • Neutrophils / metabolism
  • Oxidative Phosphorylation
  • Tumor Microenvironment / immunology*

Substances

  • Cytokines