Macrophage reprogramming for therapy

Abstract

Dysfunction of the immune system underlies a plethora of human diseases, requiring the development of immunomodulatory therapeutic intervention. To date, most strategies employed have been focusing on the modification of T lymphocytes, and although remarkable improvement has been obtained, results often fall short of the intended outcome. Recent cutting-edge technologies have highlighted macrophages as potential targets for disease control. Macrophages play central roles in development, homeostasis and host defence, and their dysfunction and dysregulation have been implicated in the onset and pathogenesis of multiple disorders including cancer, neurodegeneration, autoimmunity and metabolic diseases. Recent advancements have led to a greater understanding of macrophage origin, diversity and function, in both health and disease. Over the last few years, a variety of strategies targeting macrophages have been developed and these open new therapeutic opportunities. Here, we review the progress in macrophage reprogramming in various disorders and discuss the potential implications and challenges for macrophage-targeted approaches in human disease.

Macrophage Function in Calcium Oxalate Kidney Stone Formation: A Systematic Review of Literature

“…However, evidence regarding Mφs in urinary sediments is scant, and the direct manipulation of Mφ phenotypes for clinical use needs to be determined ( 56 ). Future investigations should strive to establish a urinary biomarker for liquid biopsies ( 57 ), and an Mφ-specific target therapy using antibodies, vectors, and nanoparticles ( 58 , 59 ).…”

Defects in Macrophage Reprogramming in Cancer Therapy: The Negative Impact of PD-L1/PD-1

“…Molecular targets for M2 macrophage reprogramming include Toll-like receptor 7 (TLR7), TLR8, TLR9, CD40, histone deacetylase (HDAC), PI3Kγ, CSF1, and CSF1 receptor (CSF1R) ( 10 ). TLR agonists induce M1 polarization and exert an anti-tumor effect via the increased release of pro-inflammatory mediators.…”

“…TLR agonists induce M1 polarization and exert an anti-tumor effect via the increased release of pro-inflammatory mediators. CD40 agonists increase the expression of co-stimulatory and antigen-presenting molecules on macrophages and the secretion of pro-inflammatory mediators, which enhances the T cell–dependent anti-tumor effect ( 10 ). TLR signaling and CD40 are known to be activated by IFN-γ ( 11 , 12 ), which is a driver of M1 polarization.…”

“…Both HDAC and PI3Kγ are involved in the M2 polarization of macrophages, providing intracellular targets for macrophage reprogramming. The inhibition of HDAC or PI3Kγ exerts an anti-tumor effect via the downregulation of M2 and upregulation of M1 molecules ( 10 ). As has been reported, PI3K is present downstream of CSF1R and is epigenetically activated during M2 polarization ( 13 ).…”

Can we treat inflammation by managing misbehaving monocytes?

“…These developments have been mirrored by exciting new insights into human MNP populations, revealing not only broadly similar biology, but also important and interesting differences [2]. An important aim of this field is to identify ways in which these cells can be manipulated, perhaps to improve responses to vaccination, or to reduce the damage caused by unwanted inflammation [3].…”