Metabolic Plasticity of Neutrophils: Relevance to Pathogen Responses and Cancer.

Children's Medical Center Research Institute, University of Texas (UT) Southwestern Medical Center, Dallas, TX, USA. Children's Medical Center Research Institute, University of Texas (UT) Southwestern Medical Center, Dallas, TX, USA; Howard Hughes Medical Institute, UT Southwestern Medical Center, Dallas, TX, USA. Electronic address: ralph.deberardinis@utsouthwestern.edu.

Trends in cancer. 2021;(8):700-713

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.

Methodological quality

Publication Type : Review

Metadata