Role of Myeloid-Derived Suppressor Cells and Regulatory T-Cells in the Tuberculous Granuloma

2019 ◽  
pp. 63-93
Author(s):  
Laurene S. Cheung ◽  
Geetha Srikrishna ◽  
William R. Bishai
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Suppressor Cells ◽  
Myeloid Derived Suppressor Cells ◽  
Tuberculous Granuloma

501 VISTA regulates the differentiation and suppressive function of myeloid-derived suppressor cells

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A536-A536
Author(s):  
Juan Dong ◽  
Cassandra Gilmore ◽  
Hieu Ta ◽  
Keman Zhang ◽  
Sarah Stone ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Signaling Pathways ◽  
Immune Checkpoint ◽  
Suppressor Cells ◽  
Myeloid Cell ◽  
Myeloid Derived Suppressor Cells ◽  
Checkpoint Protein ◽  
Suppressive Function

BackgroundV-domain immunoglobulin suppressor of T cell activation (VISTA) is a B7 family inhibitory immune checkpoint protein and is highly expressed on myeloid cells and T cells.1 VISTA acts as both an inhibitory ligand when expressed on antigen-presenting cells and a receptor when expressed on T cells. Our recent study has shown that VISTA is a myeloid cell-specific immune checkpoint and that blocking VISTA can reprogram suppressive myeloid cells and promote a T cell-stimulatory tumor microenvironment.2 In this study, we further demonstrate that VISTA blockade directly alters the differentiation and the suppressive function of myeloid-derived suppressor cells (MDSC).MethodsFlow cytometry was performed to examine VISTA expression on MDSCs in multiple murine tumor models including the B16BL6 melanoma model, MC38 colon cancer model, and the KPC pancreatic cancer models. To examine the role of VISTA in controlling the differentiation and suppressive function of MDSCs, we cultured wild type (WT) and VISTA.KO bone marrow progenitor cells with GM-CSF and IL-6 to induce BM -derived MDSCs.ResultsOur preliminary results show that VISTA is highly expressed on M-MDSCs in B16BL6, MC38 and KPC tumors. In BM-derived MDSCs, VISTA deletion significantly altered the signaling pathways and the differentiation of MDSCs. Multiple inflammatory signaling pathways were downregulated in VISTA KO MDSCs, resulting in decreased production of cytokines such as IL1 and chemokines such as CCL2/4/9, as well as significantly impaired their ability to suppress the activation of CD8+ T cells. The loss of suppressive function in VISTA KO MDSCs is correlated with significantly reduced expression of iNOS. To validate the results from BM-MDSCs, we sorted CD11b+CD11c-Ly6C+Ly6G- M-MDSCs and CD11b+CD11c-Ly6G+ G-MDSCs from B16BL6 tumor tissues and tested the ability of a VISTA-blocking mAb to reverse the suppressive effects of tumor-derived MDSCs. Our results show that blocking VISTA impaired the suppressive function of tumor-derived M-MDSC but not G-MDSCs.ConclusionsTaken together, these results demonstrate a crucial role of VISTA in regulating the differentiation and function of MDSCs, and that blocking VISTA abolishes MDSC-mediated T cell suppression, thereby boosting.Ethics ApprovalAll in vivo studies were reviewed and approved by Institutional Animal Care and Use Committee (Approval number 2019-2142).ReferencesXu W, Hire T, Malarkannan, S. et al. The structure, expression, and multifaceted role of immune-checkpoint protein VISTA as a critical regulator of anti-tumor immunity, autoimmunity, and inflammation. Cell Mol Immunol 2018;15:438–446.Xu W, Dong J, Zheng Y, et al. Immune-checkpoint protein VISTA regulates antitumor immunity by controlling myeloid cell-mediated inflammation and immunosuppression. Cancer Immunol Res 2019;7:1497–510.

scholarly journals The level of myeloid-derived suppressor cells positively correlates with regulatory T cells in the blood of children with transient hypogammaglobulinaemia of infancy

2018 ◽  
Vol 43 (4) ◽  
pp. 413-420 ◽  
Author(s):  
Izabela Siemińska ◽  
Magdalena Rutkowska-Zapała ◽  
Karolina Bukowska-Strakova ◽  
Anna Gruca ◽  
Anna Szaflarska ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Suppressor Cells ◽  
Myeloid Derived Suppressor Cells

Myeloid-Derived Suppressor Cells Predict Survival of Patients with Advanced Melanoma: Comparison with Regulatory T Cells and NY-ESO-1- or Melan-A–Specific T Cells

2013 ◽  
Vol 20 (6) ◽  
pp. 1601-1609 ◽  
Author(s):  
Benjamin Weide ◽  
Alexander Martens ◽  
Henning Zelba ◽  
Christina Stutz ◽  
Evelyna Derhovanessian ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Suppressor Cells ◽  
Advanced Melanoma ◽  
Myeloid Derived Suppressor Cells

scholarly journals The immunosuppressive tumour network: myeloid-derived suppressor cells, regulatory T cells and natural killer T cells

Immunology ◽  
2013 ◽  
Vol 138 (2) ◽  
pp. 105-115 ◽  
Author(s):  
Dennis Lindau ◽  
Paul Gielen ◽  
Michiel Kroesen ◽  
Pieter Wesseling ◽  
Gosse J. Adema
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Natural Killer ◽  
Suppressor Cells ◽  
Natural Killer T Cells ◽  
Myeloid Derived Suppressor Cells ◽  
Killer T Cells ◽  
Natural Killer T
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