Myeloid-derived suppressor cells accumulate among myeloid cells contributing to tumor growth in matrix metalloproteinase 12 knockout mice

2018 ◽  
Vol 327 ◽  
pp. 1-12 ◽  
Author(s):  
Jiangchao Li ◽  
Xiaohan Zhang ◽  
Qing Liu ◽  
Mingming Yang ◽  
Zijun Zhou ◽  
...  
2019 ◽  
Vol 217 (2) ◽  
Author(s):  
Dehong Yan ◽  
Jinghui Wang ◽  
Honghong Sun ◽  
Ali Zamani ◽  
Honglin Zhang ◽  
...  

Myeloid-derived suppressor cells (MDSCs) are “polarized” myeloid cells that effectively promote tumorigenesis by inhibiting antitumor immunity. How myeloid cells acquire the protumoral properties during tumorigenesis is poorly understood. We report here that the polarity protein TIPE2 (tumor necrosis factor-α–induced protein 8-like 2) mediates the functional polarization of murine and human MDSCs by specifying their pro- and antitumoral properties. Tumor cells induced the expression of TIPE2 in Gr1+CD11b+ cells through reactive oxygen species (ROS). TIPE2 in turn increased the expression of protumoral mediators such as CCAAT/enhancer-binding protein-β while inhibiting the expression of antitumoral mediators. Consequently, tumor growth in TIPE2-deficient mice was significantly diminished, and TIPE2-deficient MDSCs markedly inhibited tumor growth upon adoptive transfer. Pharmaceutical blockade of ROS inhibited TIPE2 expression in MDSCs and reduced tumor growth in mice. These findings indicate that TIPE2 plays a key role in the functional polarization of MDSCs and represents a new therapeutic target for cancer immunotherapy.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Clémence Marais ◽  
Caroline Claude ◽  
Nada Semaan ◽  
Ramy Charbel ◽  
Simon Barreault ◽  
...  

Abstract Background De-regulated host response to severe coronavirus disease 2019 (COVID-19), directly referring to the concept of sepsis-associated immunological dysregulation, seems to be a strong signature of severe COVID-19. Myeloid cells phenotyping is well recognized to diagnose critical illness-induced immunodepression in sepsis and has not been well characterized in COVID-19. The aim of this study is to review phenotypic characteristics of myeloid cells and evaluate their relations with the occurrence of secondary infection and mortality in patients with COVID-19 admitted in an intensive care unit. Methods Retrospective analysis of the circulating myeloid cells phenotypes of adult COVID-19 critically ill patients. Phenotyping circulating immune cells was performed by flow cytometry daily for routine analysis and twice weekly for lymphocytes and monocytes subpopulations analysis, as well as monocyte human leukocyte antigen (mHLA)-DR expression. Results Out of the 29 critically ill adult patients with severe COVID-19 analyzed, 12 (41.4%) developed secondary infection and six patients died during their stay. Monocyte HLA-DR kinetics was significantly different between patients developing secondary infection and those without, respectively, at day 5–7 and 8–10 following admission. The monocytes myeloid-derived suppressor cells to total monocytes ratio was associated with 28- and 60-day mortality. Those myeloid characteristics suggest three phenotypes: hyperactivated monocyte/macrophage is significantly associated with mortality, whereas persistent immunodepression is associated with secondary infection occurrence compared to transient immunodepression. Conclusions Myeloid phenotypes of critically ill COVID-19 patients may be associated with development of secondary infection, 28- and 60-day mortality.


Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Xiao Z Shen ◽  
Peng Shi ◽  
Jorge Giani ◽  
Ellen Bernstein ◽  
Kenneth E Bernstein

The immune system plays a critical role in the development of hypertension. The immune response consists of pro-inflammatory cells, but also immunosuppressive cells that reduce T cell function. An important category of natural immunosuppressive cell is myeloid-derived suppressor cells (MDSC). We now show that blood and spleen CD11b+ Gr1+ myeloid cells are elevated 2-fold in both angiotensin II and L-NAME induced hypertension. These increased myeloid cells are MDSC in that they elevate IL-4R expression and suppress T cell proliferation. When hypertensive mice were depleted of MDSC, using either anti-Gr1 antibody or gemcitabine, there was a 15 mmHg rise in blood pressure and aggravation of T cells activation with increased production of IFN-γ, TNFα and IL-17 in both spleen and kidney. In contrast, adoptive transfer of MDSC reduced blood pressure in angiotensin-II induced hypertension by 25 mmHg (see Figure). These data suggest a new concept, that the accumulation of MDSC is a compensatory response to the inflammation induced by hypertension. They also indicate that MDSC play an important role in regulating blood pressure.


2015 ◽  
Vol 75 (21) ◽  
pp. 4517-4526 ◽  
Author(s):  
Felipe Vences-Catalán ◽  
Ranjani Rajapaksa ◽  
Minu K. Srivastava ◽  
Aurelien Marabelle ◽  
Chiung-Chi Kuo ◽  
...  

2012 ◽  
Vol 19 (1) ◽  
pp. 57-64 ◽  
Author(s):  
Mélanie Bruchard ◽  
Grégoire Mignot ◽  
Valentin Derangère ◽  
Fanny Chalmin ◽  
Angélique Chevriaux ◽  
...  

2010 ◽  
Author(s):  
Jonathan Mitchem ◽  
Matthew Porembka ◽  
William G. Hawkins ◽  
Simon Peter Goedegebuure ◽  
David C. Linehan

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