Myeloid-derived suppressor cells in glioma

Abstract

Glioblastoma is the most prevalent form of gliomas with high aggressive nature and high recurrence. Despite aggressive therapy, including surgery, chemotherapy and radiotherapy, median patient survival is only about 15 months. Hence, developing novel and efficient therapies seem urgent. Many fields have begun their work in preclinical studies but gained limited success in clinical phases. One of the most notable reasons is tumor-induced immunosuppression. In recent decade, efforts to dissect this immunosuppressive network have been done vastly. In a number of malignancies such as glioma, myeloid-derived suppressor cells (MDSCs) have been shown to infiltrate malignant tissues having critical role in the network. Many studies, most of them on lab models, were conducted to understand how MDSCs take part in immunosuppression. Here, we reviewed MDSC relations with other immunocellular components like T cell and natural killer cell.

Keywords::

• glioblastoma
• glioma
• myeloid-derived suppressor cells

Acknowledgements

The authors would like to acknowledge AB Frey, Department of Cell Biology, New York University School of Medicine, USA, and I Poschke, DKFZ – German Cancer Research Centre, Division of Molecular Oncology of Gastrointestinal Tumors, Heidelberg, Germany, for critical reading of this paper.

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• • Immunotherapy, as a new field, which is developing rapidly, could lead to more effective treatments in cancers.

• • Tumor immunosuppressive network is one of the most challenging causes with its complex nature.

• • A heterogeneous population of immature myeloid cells, called myeloid-derived suppressor cells (MDSCs), is reported in different pathologic conditions such as autoimmune encephalitis, bacterial infections, severe traumas and many malignancies such as glioma.

• • MDSCs are known as a major part of tumor immunosuppressive network, which predominantly affects cellular immune responses.

• • In glioma, cell cycle and trafficking of T cells are the best known targets of MDSC-mediated immunosuppressive activity in glioma.

• • MDSC also influence CD8⁺ T-cells response to antigen-specific stimulation, activation and expansion of Treg cells, and natural killer cell response and its cytotoxicity in lab models and many malignancies.

• • Dissection of this network into separate meaningful pathways makes it possible to manipulate it through augmentation or attenuation of these pathways and provide beneficent antitumor immunity alongside with much better survival for glioma patients.