Targeting myeloid-derived suppressor cells to bypass tumor-induced immunosuppression
- 1Skin Cancer Unit, Deutsches Krebsforschungszentrum (DKFZ), Germany
- 2Department of Dermatology, Venereology and Allergology, Medizinische Fakultät Mannheim, Universität Heidelberg, Germany
The immune system has many sophisticated mechanisms to balance an extensive immune response. Distinct immunosuppressive cells could protect from excessive tissue damage and autoimmune disorders. Tumor cells take an advantage of those immunosuppressive mechanisms and establish a strongly immunosuppressive tumor microenvironment (TME), which inhibits anti-tumor immune responses, supporting the disease progression. Myeloid-derived suppressor cells (MDSC) play a crucial role in this immunosuppressive TME. Those cells represent a heterogeneous population of immature myeloid cells with a strong immunosuppressive potential. They inhibit an anti-tumor reactivity of T cells and NK cells. Furthermore, they promote angiogenesis, establish pre-metastatic niches and recruit other immunosuppressive cells such as regulatory T cells. Accumulating evidences demonstrated that the enrichment and activation of MDSC correlated with tumor progression, recurrence, and negative clinical outcome. In the last few years, various pre-clinical studies and clinical trials targeting MDSC showed promising results. In this review, we discuss different therapeutic approaches on MDSC targeting to overcome immunosuppressive TME and enhance the efficiency of current tumor immunotherapies.
Keywords: myeloid-derived suppressor cells, Immunosuppression, cancer immunotherapy, Tumor Microenvironment, Therapeutic targeting
Received: 30 Nov 2017;
Accepted: 13 Feb 2018.
Edited by:Salem Chouaib, Institut Gustave Roussy, France
Reviewed by:Susanna Mandruzzato, Università degli Studi di Padova, Italy
Nicolas Larmonier, Université de Bordeaux, France
Copyright: © 2018 Fleming, Hu, Weber, Nagibin, Groth, Altevogt, Utikal and Umansky. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Prof. Viktor Umansky, Deutsches Krebsforschungszentrum (DKFZ), Skin Cancer Unit, Im Neuenheimer Feld 280, Heidelberg, 69120, Germany, V.Umansky@dkfz-heidelberg.de