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MDSC in Mice and Men: Mechanisms of Immunosuppression in Cancer
Christophe Vanhaver1, Pierre van der Bruggen1,2, Annika M Bruger1
1De Duve Institute, Université Catholique de Louvain, Avenue Hippocrate 74, 1200 Brussels, Belgium.
Abstract:
Myeloid-derived suppressor cells (MDSCs) expand during pathological conditions in both humans and mice and their presence is linked to poor clinical outcomes for cancer patients. Studying MDSC immunosuppression is restricted by MDSCs' rarity, short lifespan, heterogeneity, poor viability after freezing and the lack of MDSC-specific markers. In this review, we will compare identification and isolation strategies for human and murine MDSCs. We will also assess what direct and indirect immunosuppressive mechanisms have been attributed to MDSCs. While some immunosuppressive mechanisms are well-documented in mice, e.g., generation of ROS, direct evidence is still lacking in humans. In future, bulk or single-cell genomics could elucidate which phenotypic and functional phenotypes MDSCs adopt in particular microenvironments and help to identify potential targets for therapy.
Insights
Myeloid-derived suppressor cells (MDSCs) are linked to poor cancer outcomes. This review compares strategies for studying these cells and their immunosuppressive roles, highlighting knowledge gaps in humans.
Area of Science:
- Immunology
- Cancer Biology
- Cellular Biology
Background:
- Myeloid-derived suppressor cells (MDSCs) are immune cells that accumulate in pathological conditions, including cancer.
- Their presence correlates with negative clinical outcomes in cancer patients.
- Studying MDSCs is challenging due to their rarity, short lifespan, heterogeneity, and poor cryopreservation viability.
Purpose of the Study:
- To compare methods for identifying and isolating human and murine MDSCs.
- To review the known direct and indirect immunosuppressive mechanisms of MDSCs.
- To highlight discrepancies in understanding MDSC function between mouse models and human patients.
Main Methods:
- Literature review comparing human and murine MDSC identification and isolation techniques.
- Assessment of documented MDSC-mediated immunosuppressive mechanisms.
- Analysis of current research limitations and future directions.
Main Results:
- Various strategies exist for MDSC isolation, but challenges remain due to cell characteristics.
- MDSCs employ diverse mechanisms to suppress anti-tumor immunity, such as reactive oxygen species (ROS) generation.
- While mouse studies provide insights, direct evidence for some MDSC immunosuppressive mechanisms in humans is limited.
Conclusions:
- Effective MDSC research requires robust identification and isolation methods.
- Further investigation is needed to fully elucidate human MDSC immunosuppressive functions.
- Genomic approaches may reveal therapeutic targets by defining MDSC phenotypes in specific microenvironments.
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