scholarly journals Targeting myeloid-derived suppressor cells with colony stimulating factor-1 receptor blockade can reverse immune resistance to immunotherapy in indoleamine 2,3-dioxygenase-expressing tumors

EBioMedicine ◽  
2016 ◽  
Vol 6 ◽  
pp. 50-58 ◽  
Author(s):  
Rikke B. Holmgaard ◽  
Dmitriy Zamarin ◽  
Alexander Lesokhin ◽  
Taha Merghoub ◽  
Jedd D. Wolchok
Keyword(s):  
Suppressor Cells ◽  
Receptor Blockade ◽  
Myeloid Derived Suppressor Cells ◽  
Colony Stimulating Factor ◽  
Indoleamine 2,3 Dioxygenase ◽  
Immune Resistance ◽  
Stimulating Factor

scholarly journals Bone marrow myeloid-derived suppressor cells (MDSCs) inhibit graft-versus-host disease (GVHD) via an arginase-1–dependent mechanism that is up-regulated by interleukin-13

Blood ◽  
2010 ◽  
Vol 116 (25) ◽  
pp. 5738-5747 ◽  
Author(s):  
Steven L. Highfill ◽  
Paulo C. Rodriguez ◽  
Qing Zhou ◽  
Christine A. Goetz ◽  
Brent H. Koehn ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cell ◽  
Graft Versus Host Disease ◽  
Suppressor Cells ◽  
Myeloid Derived Suppressor Cells ◽  
Colony Stimulating Factor ◽  
Graft Versus Host ◽  
Arginase 1 ◽  
Stimulating Factor ◽  
Pegylated Form

Abstract Myeloid-derived suppressor cells (MDSCs) are a well-defined population of cells that accumulate in the tissue of tumor-bearing animals and are known to inhibit immune responses. Within 4 days, bone marrow cells cultured in granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor resulted in the generation of CD11b+Ly6GloLy6C+ MDSCs, the majority of which are interleukin-4Rα (IL-4Rα+) and F4/80+. Such MDSCs potently inhibited in vitro allogeneic T-cell responses. Suppression was dependent on L-arginine depletion by arginase-1 activity. Exogenous IL-13 produced an MDSC subset (MDSC-IL-13) that was more potently suppressive and resulted in arginase-1 up-regulation. Suppression was reversed with an arginase inhibitor or on the addition of excess L-arginine to the culture. Although both MDSCs and MDSC-IL-13 inhibited graft-versus-host disease (GVHD) lethality, MDSC-IL-13 were more effective. MDSC-IL-13 migrated to sites of allopriming. GVHD inhibition was associated with limited donor T-cell proliferation, activation, and proinflammatory cytokine production. GVHD inhibition was reduced when arginase-1-deficient MDSC-IL-13 were used. MDSC-IL-13 did not reduce the graft-versus-leukemia effect of donor T cells. In vivo administration of a pegylated form of human arginase-1 (PEG-arg1) resulted in L-arginine depletion and significant GVHD reduction. MDSC-IL-13 and pegylated form of human arginase-1 represent novel strategies to prevent GVHD that can be clinically translated.

scholarly journals Dendritic Cells and Myeloid Derived Suppressor Cells Fully Responsive to Stimulation via Toll-Like Receptor 4 Are Rapidly Induced from Bone-Marrow Cells by Granulocyte-Macrophage Colony-Stimulating Factor

Vaccines ◽  
2020 ◽  
Vol 8 (3) ◽  
pp. 522
Author(s):  
Ying Ying Kong ◽  
Kirsty Wilson ◽  
Vasso Apostolopoulos ◽  
Magdalena Plebanski
Keyword(s):  
Bone Marrow ◽  
Suppressor Cells ◽  
Myeloid Derived Suppressor Cells ◽  
Colony Stimulating Factor ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Gm Csf ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

Dendritic cells (DCs) are commonly generated from bone marrow (BM) progenitor cells with granulocyte-macrophage colony-stimulating factor (GM-CSF) alone or in combination with interleukin 4 (IL-4). These cells are often harvested post day 5, when they acquire maturation markers and can stimulate T cells. Apart from DCs, myeloid derived suppressor cells (MDSCs) are also found within these cultures. However, little is known about the functional characteristics of DCs and MDSCs before day 5. Herein, using a murine model, it is shown that early DCs and MDSCs, even in cultures with GM-CSF alone, upregulate fully maturation and activation surface molecules in response to the toll-like receptor 4 (TLR4) ligand lipopolysaccharide (LPS) stimulation. Despite initially displaying lower marker expression levels, these cells efficiently induced T cell stimulation and cytokine production. Interestingly, Gr-1int MDSCs increased their T cell co-stimulatory activity upon TLR4 stimulation. Additionally, early DCs and MDSCs exhibited differential endocytic capacity for viral sized nanoparticles and bacterial sized microparticles. DCs internalized both particle sizes, whilst MDSCs only internalized the larger microparticles, with reduced endocytic activity over time in the culture. These findings have unveiled an important role for the rapid initiation of productive immunity by GM-CSF, with promising implications for future vaccine and DC immunotherapy developments.

scholarly journals May critical molecular cross-talk between indoleamine 2,3-dioxygenase (IDO) and arginase during human aging be targets for immunosenescence control?

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Ismael Dale Cotrim Guerreiro da Silva ◽  
Dirce Maria Lobo Marchioni ◽  
Antonio Augusto Ferreira Carioca ◽  
Valquiria Bueno ◽  
Gisele Wally Braga Colleoni
Keyword(s):  
Immune System ◽  
Aging Process ◽  
Methylation Status ◽  
Suppressor Cells ◽  
Myeloid Derived Suppressor Cells ◽  
Beta Oxidation ◽  
Blood Concentrations ◽  
Indoleamine 2,3 Dioxygenase ◽  
Mass Spectrometry Technology ◽  
Peripheral Blood Plasma

Abstract Background This study aimed to identify novel plasma metabolic signatures with possible clinical relevance during the aging process. A biochemical quantitative phenotyping platform, based on targeted electrospray ionization tandem mass spectrometry technology, was used for the identification of any eventual perturbed biochemical pathway by the aging process in prospectively collected peripheral blood plasma from 166 individuals representing the population of São Paulo city, Brazil. Results Indoleamine 2,3-dioxygenase (IDO) activity (Kyn/Trp) was significantly elevated with age, and among metabolites most associated with elevations in IDO, one of the strongest correlations was with arginase (Orn/Arg), which could also facilitate the senescence process of the immune system. Hyperactivity of IDO was also found to correlate with increased blood concentrations of medium-chain acylcarnitines, suggesting that deficiencies in beta-oxidation may also be involved in the immunosenescence process. Finally, our study provided evidence that the systemic methylation status was significantly increased and positively correlated to IDO activity. Conclusions In the present article, besides identifying elevated IDO activity exhibiting striking parallel association with the aging process, we additionally identified increased arginase activity as an underlying biochemical disturbance closely following elevations in IDO. Our findings support interventions to reduce IDO or arginase activities in an attempt to preserve the functionality of the immune system, including modulation of myeloid-derived suppressor cells (MDSCs), T cells, macrophages, and dendritic cells’ function, in old individuals/patients.

scholarly journals Colony-stimulating factor (CSF) 1 receptor blockade reduces inflammation in human and murine models of rheumatoid arthritis

2016 ◽  
Vol 18 (1) ◽  
Author(s):  
Samuel Garcia ◽  
Linda M. Hartkamp ◽  
B Malvar-Fernandez ◽  
Inge E. van Es ◽  
Haishan Lin ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Receptor Blockade ◽  
Murine Models ◽  
Colony Stimulating Factor ◽  
Stimulating Factor
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