The Role of PGE2 in the Induction of Suppressor Cells in Humans

1985 ◽  
pp. 55-78 ◽  
Author(s):  
A. Fischer ◽  
A. Durandy ◽  
F. Le Deist ◽  
C. Griscelli
Keyword(s):  
Suppressor Cells

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 Role of Myeloid-Derived Suppressor Cells (MDSC) in Cancer Progression

Vaccines ◽  
2016 ◽  
Vol 4 (4) ◽  
pp. 36 ◽  
Author(s):  
Viktor Umansky ◽  
Carolin Blattner ◽  
Christoffer Gebhardt ◽  
Jochen Utikal
Keyword(s):  
Cancer Progression ◽  
Suppressor Cells ◽  
Myeloid Derived Suppressor Cells

ROLE OF SUPPRESSOR CELLS IN IMMUNOLOGICAL MATURATION1

1981 ◽  
Vol 31 (5) ◽  
pp. 334-338 ◽  
Author(s):  
BERTIE F. ARGYRIS
Keyword(s):  
Suppressor Cells

scholarly journals The critical immunosuppressive effect of MDSC-derived exosomes in the tumor microenvironment

2020 ◽  
Author(s):  
Mohammad H. Rashid ◽  
Thaiz F. Borin ◽  
Roxan Ara ◽  
Raziye Piranlioglu ◽  
Bhagelu R. Achyut ◽  
...  
Keyword(s):  
T Cells ◽  
Tumor Microenvironment ◽  
Tumor Growth ◽  
Cd8 T Cells ◽  
Suppressor Cells ◽  
Cell Types ◽  
Biological Macromolecules

AbstractMyeloid-derived suppressor cells (MDSCs) are an indispensable component of the tumor microenvironment (TME), and our perception regarding the role of MDSCs in tumor promotion is attaining extra layer of intricacy in every study. In conjunction with MDSC’s immunosuppressive and anti-tumor immunity, they candidly facilitate tumor growth, differentiation, and metastasis in several ways that yet to be explored. Alike any other cell types, MDSCs also release a tremendous amount of exosomes or nanovesicles of endosomal origin and partake in intercellular communications by dispatching biological macromolecules. There has not been any experimental study done to characterize the role of MDSCs derived exosomes (MDSC exo) in the modulation of TME. In this study, we isolated MDSC exo and demonstrated that they carry a significant amount of proteins that play an indispensable role in tumor growth, invasion, angiogenesis, and immunomodulation. We observed higher yield and more substantial immunosuppressive potential of exosomes isolated from MDSCs in the primary tumor area than those are in the spleen or bone marrow. Our in vitro data suggest that MDSC exo are capable of hyper activating or exhausting CD8 T-cells and induce reactive oxygen species production that elicits activation-induced cell death. We confirmed the depletion of CD8 T-cells in vivo by treating the mice with MDSC exo. We also observed a reduction in pro-inflammatory M1-macrophages in the spleen of those animals. Our results indicate that immunosuppressive and tumor-promoting functions of MDSC are also implemented by MDSC-derived exosomes which would open up a new avenue of MDSC research and MDSC-targeted therapy.

scholarly journals Regulatory Immune Cells in Idiopathic Pulmonary Fibrosis: Friends or Foes?

2021 ◽  
Vol 12 ◽  
Author(s):  
Chiel van Geffen ◽  
Astrid Deißler ◽  
Markus Quante ◽  
Harald Renz ◽  
Dominik Hartl ◽  
...  
Keyword(s):  
Immune System ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Immune Responses ◽  
Immune Cells ◽  
Current Knowledge ◽  
Suppressor Cells ◽  
Interstitial Lung Diseases ◽  
Stromal Stem Cells

The immune system is receiving increasing attention for interstitial lung diseases, as knowledge on its role in fibrosis development and response to therapies is expanding. Uncontrolled immune responses and unbalanced injury-inflammation-repair processes drive the initiation and progression of idiopathic pulmonary fibrosis. The regulatory immune system plays important roles in controlling pathogenic immune responses, regulating inflammation and modulating the transition of inflammation to fibrosis. This review aims to summarize and critically discuss the current knowledge on the potential role of regulatory immune cells, including mesenchymal stromal/stem cells, regulatory T cells, regulatory B cells, macrophages, dendritic cells and myeloid-derived suppressor cells in idiopathic pulmonary fibrosis. Furthermore, we review the emerging role of regulatory immune cells in anti-fibrotic therapy and lung transplantation. A comprehensive understanding of immune regulation could pave the way towards new therapeutic or preventive approaches in idiopathic pulmonary fibrosis.

Depressedin vitro peripheral blood lymphocyte response to mitogens in cancer patients: The role of suppressor cells

1977 ◽  
Vol 19 (5) ◽  
pp. 605-613 ◽  
Author(s):  
Marek Zembala ◽  
Bozena Mytar ◽  
Tadeusz Popiela ◽  
Geoffrey L. Asherson
Keyword(s):  
Cancer Patients ◽  
Peripheral Blood Lymphocyte ◽  
Peripheral Blood ◽  
Blood Lymphocyte ◽  
Suppressor Cells ◽  
Lymphocyte Response

AGE-RELATED DECLINE IN VACCINATION EFFICACY: THE POTENTIAL ROLE OF MYELOID DERIVED SUPPRESSOR CELLS

2020 ◽  
pp. 785-795
Author(s):  
Ю. В. Перфильева ◽  
Б. В. Каральник ◽  
Е. О. Остапчук ◽  
А. Кали ◽  
Р. Т. Тлеулиева ◽  
...  
Keyword(s):  
Young People ◽  
Infectious Diseases ◽  
Older People ◽  
Suppressor Cells ◽  
Primary Response ◽  
Myeloid Derived Suppressor Cells ◽  
Age Related ◽  
Cellular And Humoral Immunity

Инфекционные заболевания у пожилых людей значительно более часты и смертность от них выше, чем у молодых людей. Вакцинация является наиболее эффективной и наименее затратной профилактической мерой при ряде инфекционных заболеваний. Однако вакцины, которые эффективны у молодых людей, часто неэффективны у пожилых людей старше 65 лет, причиной чего является постепенное снижение функциональных возможностей иммунной системы, происходящее с возрастом и называемое иммуностарением. Связанные с возрастом изменения в клеточном и гуморальном иммунитете ухудшают первичный ответ на вакцины и ослабляют развитие долговременной иммунной памяти. Исследования последних лет дают основание предполагать, что одной из возможных причин возникновения и поддержания иммуностарения в организме могут быть миелоидные супрессорные клетки ( Myeloid-Derived Suppressor Cells, MDSC ). Многочисленными исследованиями установлено, что MDSC способны ингибировать функции клеток врожденного и адаптивного иммунитета посредством ряда механизмов. В настоящем обзоре приводятся сведения, подчеркивающие роль MDSC в ингибировании иммунного ответа на вакцины при старении, а также обосновываются возможные пути преодоления данного иммунного препятствия. Infectious diseases in older people are much more frequent, and mortality from them is higher than in young people. Vaccination is the most effective and least expensive preventative measure for a number of infectious diseases. However, vaccines that are effective in young people are often ineffective in older people over 65, which is a result of a gradual decrease in the functional capacity of the immune systems, which occurs with age, and is called «immunosenescence». Age-related changes in the cellular and humoral immunity worsen the primary response to vaccines and weaken the development of long-term immunological memory. Recent studies suggest that one of the possible causes of the occurrence and maintenance of «immunosenescence» may be myeloid-derived suppressor cells ( MDSCs ). These cells have been shown to inhibit the functions of innate and adaptive immunity cells through a number of mechanisms. In this review, we provide information that emphasizes the role of MDSCs in inhibiting the immune response to vaccines during aging, and also substantiates possible ways to overcome this immunological obstacle.

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