Therapeutic prospects of targeting myeloid-derived suppressor cells and immune checkpoints in cancer

2018 ◽  
Vol 96 (9) ◽  
pp. 888-897 ◽  
Author(s):  
Salman M Toor ◽  
Eyad Elkord
2018 ◽  
Vol 12 (1) ◽  
pp. 455-465 ◽  
Author(s):  
Nobuo Kondoh ◽  
Masako Mizuno-Kamiya ◽  
Eiji Takayama ◽  
Harumi Kawati ◽  
Naoki Umemura ◽  
...  

Introduction:In order to survive, cancers control immune systems and evade immune detection using mediators consisting of immune checkpoint molecules and cellular systems associated with immune suppression.Methodology:During the development of cancer and chronic infections, the immune checkpoints and cellular components including regulatory T cells, myeloid derived suppressor cells and cancer associated fibroblasts are often enhanced as a mechanism of immune subversion and have therefore become very important therapeutic targets.Conclusion:In this review, we will discuss the complexity of immune-suppressive mechanisms in the tumor milieu of cancers, including oral malignancy.


2018 ◽  
Vol 72 ◽  
pp. 1179-1198
Author(s):  
Natalia Anger ◽  
Joanna Rossowska

Myeloid-derived suppressor cells are heterogenic immature myeloid cells, which possess suppressor activity and play an important role in both, tumor progression and metastasis. The accumulation of MDSCs is induced primarily by factors that are secreted by the tumor microenvironment, which disturb myelopoiesis that occurs in the bone marrow and enables the migration of immature myeloid cells into the tumor. MDSCs promote tumor growth by inhibiting the activity of immunocompetent cells, as well as by activating non-immunological processes, such as tumor angiogenesis, the degradation of extracellular matrix and the formation of premetastatic niche. Due to their significant impact on the development of cancer, MDSCs became clinically relevant in tumor diagnostics. In recent years, various therapeutic strategies were developed in order to inhibit the proliferation, accumulation or suppressor activity of MDSCs, as well as to render the differentiation or total depletion of these cells. The proposed therapies often combine factors that reduce MDSCs suppression with conventional chemotherapy or with immune checkpoints inhibitors. In this review, we describe the current state of knowledge about factors that enable the accumulation of MDSCs, methods of phenotypic identification of these cells, as well as the mechanisms of suppression used by them. Moreover, we provide insight into the therapeutic approaches, which aim to restore the reactivity of the immune system by reducing the suppressor effects of MDSCs.


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