Myeloid-derived suppressor cells: a grey eminence in the AML tumor microenvironment?

Author(s):  
Jan Philipp Bewersdorf ◽  
Amer M Zeidan
PLoS ONE ◽  
2011 ◽  
Vol 6 (4) ◽  
pp. e18534 ◽  
Author(s):  
Kimberly C. Boelte ◽  
Laura E. Gordy ◽  
Sebastian Joyce ◽  
Mary Ann Thompson ◽  
Li Yang ◽  
...  

2020 ◽  
Author(s):  
S. Mahnaz ◽  
L. Das Roy ◽  
M. Bose ◽  
C. De ◽  
S. Nath ◽  
...  

ABSTRACTMyeloid-derived suppressor cells (MDSCs) are immature myeloid cells that are responsible for immunosuppression in tumor microenvironment. Here we report the impact of mucin 1 (MUC1), a transmembrane glycoprotein, on proliferation and functional activity of MDSCs. To determine the role of MUC1 in MDSC phenotype, we analyzed MDSCs derived from wild type (WT) and MUC1-knockout (MUC1KO) mice bearing pancreatic ductal adenocarcinoma KCKO and breast cancer C57MG xenografts. We observed enhanced tumor growth in MUC1KO mice compared to WT mice in both pancreatic KCKO and breast C57MG cancer models due to increased MDSC population and enrichment of Tregs in tumor microenvironment. Our current study shows that knockdown of MUC1 in MDSCs promotes proliferation and immature suppressive phenotype indicated by increased level of iNOS, ARG1 activity and TGF-β secretion under cancer conditions. Increased activity of MDSCs leads to repression of IL-2 and IFN-ɣ production by T-cells. We were able to find that MDSCs from MUC1KO mice have higher levels of c-Myc and activated pSTAT3 as compared to MUC1 WT mice, that are signaling pathways leading to increased survival, proliferation and prevention of maturation. In summary, MUC1 regulates signaling pathways that maintain immunosuppressive properties of MDSCs. Thus, immunotherapy must target only tumor associated MUC1 on epithelial cells and not MUC1 on hematopoietic cells to avoid expansion and suppressive functions of MDSC.


2014 ◽  
Vol 16 (suppl 5) ◽  
pp. v121-v122
Author(s):  
N. Kamran ◽  
M. Ayala ◽  
Y. Li ◽  
H. Assi ◽  
M. Candolfi ◽  
...  

2017 ◽  
Vol 66 (2) ◽  
pp. 113-123 ◽  
Author(s):  
Maria Ibáñez-Vea ◽  
Miren Zuazo ◽  
Maria Gato ◽  
Hugo Arasanz ◽  
Gonzalo Fernández-Hinojal ◽  
...  

Author(s):  
Xiantu Ou ◽  
Weibiao Lv

It is universally acknowledged that a large number of immune cells, as well as inflammatory factors, regulatory factors and metabolites, accumulate in the tumor microenvironment to jointly promote tumor escape, development and metastasis. Hypoxia is one of the characteristics in tumor microenvironment and is a common phenomenon in all solid tumors. In tumor hypoxia response, there is a key regulator called HIF-1a, which is a key transcriptional regulatory protein that regulates many critical genes. In this paper, the effects of hypoxia on glucose metabolism of tumor cells, myeloid-derived suppressor cells and T cells in tumor microenvironment were reviewed, and the interaction among the three was also described.


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