Journal ArticleDOI
Myeloid-derived suppressor cell function is reduced by Withaferin A, a potent and abundant component of Withania somnifera root extract
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TLDR
Adjunctive treatment with Withaferin A (WA) reduced myeloid cell-mediated immune suppression, polarized immunity toward a tumor-rejecting type 1 phenotype, and may facilitate the development of anti-tumor immunity.Abstract:
Myeloid cells play a crucial role in tumor progression. The most common tumor-infiltrating myeloid cells are myeloid-derived suppressor cells (MDSC) and tumor-associated macrophages (TAMs). These cells promote tumor growth by their inherent immune suppressive activity which is enhanced by their cross-talk. The root extract of the plant Withania somnifera (Ashwagandha) (WRE) has been reported to reduce tumor growth. HPLC analysis identified Withaferin A (WA) as the most abundant constituent of WRE and led us to determine whether the anti-tumor effects of WRE and WA involve modulating MDSC and TAM activity. A prominent effect of MDSC is their production of IL-10 which increases upon cross-talk with macrophages, thus polarizing immunity to a pro-tumor type 2 phenotype. In vitro treatment with WA decreased MDSC production of IL-10 and prevented additional MDSC production of IL-10 generated by MDSC–macrophage cross-talk. Macrophage secretion of IL-6 and TNFα, cytokines that increase MDSC accumulation and function, was also reduced by in vitro treatment with WA. Much of the T-cell suppressive activity of MDSC is due to MDSC production of reactive oxygen species (ROS), and WA significantly reduced MDSC production of ROS through a STAT3-dependent mechanism. In vivo treatment of tumor-bearing mice with WA decreased tumor weight, reduced the quantity of granulocytic MDSC, and reduced the ability of MDSC to suppress antigen-driven activation of CD4+ and CD8+ T cells. Thus, adjunctive treatment with WA reduced myeloid cell-mediated immune suppression, polarized immunity toward a tumor-rejecting type 1 phenotype, and may facilitate the development of anti-tumor immunity.read more
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Journal ArticleDOI
Broad targeting of angiogenesis for cancer prevention and therapy
Zongwei Wang,Charlotta Dabrosin,Xin Yin,Mark M. Fuster,Alexandra Arreola,W. Kimryn Rathmell,Daniele Generali,Ganji Purnachandra Nagaraju,Bassel F. El-Rayes,Domenico Ribatti,Yi Charlie Chen,Kanya Honoki,Hiromasa Fujii,Alexandros G. Georgakilas,Somaira Nowsheen,Amedeo Amedei,Elena Niccolai,Amr Amin,S. Salman Ashraf,Bill Helferich,Xujuan Yang,Gunjan Guha,Dipita Bhakta,Maria Rosa Ciriolo,Katia Aquilano,Sophie Chen,Dorota Halicka,Sulma I. Mohammed,Asfar S. Azmi,Alan Bilsland,W. Nicol Keith,Lasse Jensen,Lasse Jensen +32 more
TL;DR: 10 important aspects of tumor angiogenesis and the pathological tumor vasculature which would be well suited as targets for anti-angiogenic therapy are identified and 10 plant-derived compounds could be combined to constitute a broader acting and more effective inhibitory cocktail at doses that would not be likely to cause excessive toxicity.
Book ChapterDOI
Myeloid-Derived Suppressor Cells: Critical Cells Driving Immune Suppression in the Tumor Microenvironment.
TL;DR: The history and identification of M DSCs, the role of inflammation and intracellular signaling events governing MDSC accumulation and suppressive activity, immune-suppressive mechanisms utilized by MDSCs, and recent therapeutics that target MDScs to enhance antitumor immunity are described.
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Myeloid derived suppressor cells—An overview of combat strategies to increase immunotherapy efficacy
TL;DR: Effective mono- or multimodal-therapies that target MDSCs for the benefit of cancer treatment are described.
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HMGB1 Enhances Immune Suppression by Facilitating the Differentiation and Suppressive Activity of Myeloid-Derived Suppressor Cells
Katherine H. Parker,Pratima Sinha,Lucas A. Horn,Virginia K. Clements,Huan Yang,Jianhua Li,Kevin J. Tracey,Suzanne Ostrand-Rosenberg +7 more
TL;DR: HMGB1 promotes the development of MDSCs from bone marrow progenitor cells, contributing to their ability to suppress antigen-driven activation of CD4(+) and CD8(+) T cells, and increases MDSC-mediated production of IL-10, enhanced crosstalk between MDSCS and macrophages, and facilitated the ability of M DSCs to downregulate expression of the T-cell homing receptor L-selectin.
Journal ArticleDOI
Evolution of the adaptogenic concept from traditional use to medical systems: Pharmacology of stress- and aging-related diseases.
Alexander Panossian,Thomas Efferth,A.N. Shikov,Olga N. Pozharitskaya,Kenny Kuchta,Pulok K. Mukherjee,Subhadip Banerjee,Michael Heinrich,Wanying Wu,De-An Guo,Hildebert Wagner +10 more
TL;DR: The evolution of the adaptogenic concept has led back to basics of TMS and a new level of understanding of holistic approach, which provides a rationale for their use in stress‐induced and aging‐related diseases.
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