Immunomodulatory effects of G-CSF in cancer: Therapeutic implications. (April 2021)

• Record Type: Journal Article
• Authors: Mouchemore, Kellie A.; Anderson, Robin L.
• Is Part Of: Seminars in immunology. Volume 54(2021)
• Publication Date: 2021-04
• Subjects: G-CSF granulocyte colony stimulating factor -- G-CSFR granulocyte colony stimulating factor receptor -- HSC hematopoietic stem cell -- TME tumour microenvironment -- MDSC myeloid-derived suppressor cell -- TNBC triple negative breast cancer -- PD-L1 programmed death-ligand 1 -- PD-1 programmed cell death protein 1 -- NET neutrophil extracellular trap -- IL-1β interleukin 1 beta -- MPO myeloperoxidase -- LDN low density neutrophil -- HDN high density neutrophil -- H3Cit citrullinated histone H3 -- CTC circulating tumour cell -- OS overall survival -- PFS progression-free survival -- scRNA-seq single cell RNA sequencing -- PMN polymorphonuclear -- TRL tumour-related leukocytosis -- NLR neutrophil to lymphocyte ratio -- DTC disseminated tumour cell -- G-MDSC granulocytic-myeloid-derived suppressor cell -- IL-17A interleukin-17A -- PGE2 prostaglandin E2 -- CSC cancer stem cell -- IL-6 interleukin-6 -- TAM tumour-associated macrophage -- CRC colorectal cancer -- BMM bone marrow macrophage -- IL-10 interleukin-10 -- IL-12 interleukin-12 -- IFNγ interferon gamma -- CSF-1 colony-stimulating factor 1 -- GM-CSF granulocyte-macrophage colony-stimulating factor -- ER estrogen receptor -- TIL tumour-infiltrating lymphocyte -- CAIX carbonic anhydrase IX -- cDC conventional dendritic cell -- ICB immune checkpoint blockade -- haem-irAE haematological immune-related adverse events -- ROS reactive oxygen species -- VEGF vascular endothelial growth factor -- MMP-9 matrix metalloproteinase 9 -- PDAC pancreatic ductal adenocarcinoma; G-CSF -- Cancer -- Metastasis -- Therapy -- Neutrophils -- MDSCs; Immunology -- Periodicals; Allergy and Immunology -- Periodicals; Immunity -- Periodicals; Immunologie -- Périodiques; Electronic journals; 616.079
• DOI: 10.1016/j.smim.2021.101512
• Languages: English
• ISSNs: 1044-5323

Abstract

Abstract: Numerous preclinical studies have reported a pro-tumour role for granulocyte colony-stimulating factor (G-CSF) that is predominantly mediated by neutrophils and MDSCs, the major G-CSF receptor expressing populations. In the presence of G-CSF (either tumour-derived or exogenous) these myeloid populations commonly exhibit a T cell suppressive phenotype. However, the direct effects of this cytokine on other immune lineages, such as T and NK cells, are not as well established. Herein we discuss the most recent data relating to the effect of G-CSF on the major immune populations, exclusively in the context of cancer. Recent publications have drawn attention to the other tumour-promoting effects of G-CSF on myeloid cells, including NETosis, promotion of cancer stemness and skewed differentiation of bone marrow progenitors towards myelopoiesis. Although G-CSF is safely and commonly used as a supportive therapy to prevent or treat chemotherapy-associated neutropenia in cancer patients, we also discuss the potential impacts of G-CSF on other anti-cancer treatments. Importantly, considerations for immune checkpoint blockade are highlighted, as many publications report a T cell suppressive effect of G-CSF that may diminish the effectiveness of this immunotherapy.