» Articles » PMID: 33593661

Granulocyte Macrophage Colony-stimulating Factor Has Come of Age: From a Vaccine Adjuvant to Antiviral Immunotherapy

Overview
Date 2021 Feb 17
PMID 33593661
Citations 31
Authors
Affiliations
Soon will be listed here.
Abstract

GM-CSF acts as a pro-inflammatory cytokine and a key growth factor produced by several immune cells such as macrophages and activated T cells. In this review, we discuss recent studies that point to the crucial role of GM-CSF in the immune response against infections. Upon induction, GM-CSF activates four main signalling networks including the JAK/STAT, PI3K, MAPK, and NFκB pathways. Many of these transduction pathways such as JAK/STAT signal via proteins commonly activated with other antiviral signalling cascades, such as those induced by IFNs. GM-CSF also helps defend against respiratory infections by regulating alveolar macrophage differentiation and enhancing innate immunity in the lungs. Here, we also summarize the numerous clinical trials that have taken advantage of GM-CSF's mechanistic attributes in immunotherapy. Moreover, we discuss how GM-CSF is used as an adjuvant in vaccines and how its activity is interfered with to reduce inflammation such as in the case of COVID-19. This review brings forth the current knowledge on the antiviral actions of GM-CSF, the associated signalling cascades, and its application in immunotherapy.

Citing Articles

Advanced progress in the genetic modification of the oncolytic HSV-1 virus.

Zhou M, Shen Z Front Oncol. 2025; 14:1525940.

PMID: 39906660 PMC: 11790444. DOI: 10.3389/fonc.2024.1525940.


The association of maternal COVID-19-infection during pregnancy on the neonatal immune profile and associations with later diagnosis of neurodevelopmental disorders.

Kim D, Croen L, Iosif A, Ames J, Alexeeff S, Qian Y Brain Behav Immun. 2024; 123:1071-1080.

PMID: 39532198 PMC: 11684471. DOI: 10.1016/j.bbi.2024.11.014.


Benzo (A) pyrene exposure alters alveolar epithelial and macrophage cells diversity and induces antioxidant responses in lungs.

Chauhan P, Bhardwaj N, Rajaura S, Chandra H, Singh A, Babu R Toxicol Rep. 2024; 13:101777.

PMID: 39506978 PMC: 11539143. DOI: 10.1016/j.toxrep.2024.101777.


Present and Future of Immunotherapy for Triple-Negative Breast Cancer.

Sriramulu S, Thoidingjam S, Speers C, Nyati S Cancers (Basel). 2024; 16(19).

PMID: 39409871 PMC: 11475478. DOI: 10.3390/cancers16193250.


Evaluation of the immune responses of biological adjuvant bivalent vaccine with three different insertion modes for ND and IBD.

Sun W, Li S, Niu D, Qin R, Li H, Xue Z Virulence. 2024; 15(1):2387181.

PMID: 39101682 PMC: 11302549. DOI: 10.1080/21505594.2024.2387181.


References
1.
Lee M, Lacey D, Fleetwood A, Achuthan A, Hamilton J, Cook A . GM-CSF- and IRF4-Dependent Signaling Can Regulate Myeloid Cell Numbers and the Macrophage Phenotype during Inflammation. J Immunol. 2019; 202(10):3033-3040. DOI: 10.4049/jimmunol.1801549. View

2.
Cakarova L, Marsh L, Wilhelm J, Mayer K, Grimminger F, Seeger W . Macrophage tumor necrosis factor-alpha induces epithelial expression of granulocyte-macrophage colony-stimulating factor: impact on alveolar epithelial repair. Am J Respir Crit Care Med. 2009; 180(6):521-32. DOI: 10.1164/rccm.200812-1837OC. View

3.
de Groot R, Coffer P, Koenderman L . Regulation of proliferation, differentiation and survival by the IL-3/IL-5/GM-CSF receptor family. Cell Signal. 1998; 10(9):619-28. DOI: 10.1016/s0898-6568(98)00023-0. View

4.
Tuttle D, Harrison J, Anders C, Sleasman J, Goodenow M . Expression of CCR5 increases during monocyte differentiation and directly mediates macrophage susceptibility to infection by human immunodeficiency virus type 1. J Virol. 1998; 72(6):4962-9. PMC: 110058. DOI: 10.1128/JVI.72.6.4962-4969.1998. View

5.
Burmester G, McInnes I, Kremer J, Miranda P, Korkosz M, Vencovsky J . A randomised phase IIb study of mavrilimumab, a novel GM-CSF receptor alpha monoclonal antibody, in the treatment of rheumatoid arthritis. Ann Rheum Dis. 2017; 76(6):1020-1030. DOI: 10.1136/annrheumdis-2016-210624. View