Immunosuppression mediated by myeloid-derived suppressor cells (MDSCs) during tumour progression

Under steady-state conditions, bone marrow-derived immature myeloid cells (IMC) differentiate into granulocytes, macrophages and dendritic cells (DCs). This differentiation is impaired under chronic inflammatory conditions, which are typical for tumour progression, leading to the accumulation of IMC...

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Vydáno v:	British journal of cancer Ročník 120; číslo 1; s. 16 - 25
Hlavní autoři:	Groth, Christopher, Hu, Xiaoying, Weber, Rebekka, Fleming, Viktor, Altevogt, Peter, Utikal, Jochen, Umansky, Viktor
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	London Nature Publishing Group UK 08.01.2019 Nature Publishing Group
Témata:	631/250/251/1574 631/67/580/1884 Adenosine Animals Biomedical and Life Sciences Biomedicine Bone marrow Cancer Cancer immunotherapy Cancer Research Cell Differentiation - genetics Clinical trials Cytokines Dendritic cells Drug Resistance Epidemiology Humans Immune Tolerance Immunosuppression Immunosuppression - methods Immunotherapy Inflammation Leukocytes (granulocytic) Lymphocytes T Macrophages Macrophages - immunology Macrophages - pathology Metabolites Mice Molecular Medicine Myeloid cells Myeloid-Derived Suppressor Cells - immunology Neoplasms - immunology Neoplasms - therapy Oncology Review Review Article Suppressor cells T-Lymphocytes - immunology Tumor microenvironment Tumor Microenvironment - immunology Tumors
ISSN:	0007-0920, 1532-1827, 1532-1827
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Popis
Shrnutí:	Under steady-state conditions, bone marrow-derived immature myeloid cells (IMC) differentiate into granulocytes, macrophages and dendritic cells (DCs). This differentiation is impaired under chronic inflammatory conditions, which are typical for tumour progression, leading to the accumulation of IMCs. These cells are capable of inducing strong immunosuppressive effects through the expression of various cytokines and immune regulatory molecules, inhibition of lymphocyte homing, stimulation of other immunosuppressive cells, depletion of metabolites critical for T cell functions, expression of ectoenzymes regulating adenosine metabolism, and the production of reactive species. IMCs are therefore designated as myeloid-derived suppressor cells (MDSCs), and have been shown to accumulate in tumour-bearing mice and cancer patients. MDSCs are considered to be a strong contributor to the immunosuppressive tumour microenvironment and thus an obstacle for many cancer immunotherapies. Consequently, numerous studies are focused on the characterisation of MDSC origin and their relationship to other myeloid cell populations, their immunosuppressive capacity, and possible ways to inhibit MDSC function with different approaches being evaluated in clinical trials. This review analyses the current state of knowledge on the origin and function of MDSCs in cancer, with a special emphasis on the immunosuppressive pathways pursued by MDSCs to inhibit T cell functions, resulting in tumour progression. In addition, we describe therapeutic strategies and clinical benefits of MDSC targeting in cancer.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 ObjectType-Literature Review-3 ObjectType-Review-3 content type line 23
ISSN:	0007-0920 1532-1827 1532-1827
DOI:	10.1038/s41416-018-0333-1