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MDSC – Myeloid-derived Suppressor Cells Explained

MDSC (Myeloid-derived Suppressor Cells) are immature myeloid cells that suppress immune responses and play a key role in cancer, chronic infections, and inflammatory diseases.

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Things worth knowing about "MDSC"

MDSC (Myeloid-derived Suppressor Cells) are immature myeloid cells that suppress immune responses and play a key role in cancer, chronic infections, and inflammatory diseases.

What Are MDSC?

MDSC (Myeloid-derived Suppressor Cells) are a heterogeneous population of immature myeloid cells that expand significantly under pathological conditions – particularly in cancer, chronic infections, and autoimmune diseases. They are among the most important immunosuppressive cell populations in the human body and are the subject of intense biomedical research worldwide.

Origin and Classification

MDSC originate from hematopoietic progenitor cells in the bone marrow. Under normal circumstances, these precursor cells mature into macrophages, dendritic cells, or granulocytes. In disease states, this maturation process is blocked, resulting in the accumulation of immature cells with potent immunosuppressive activity.

Two main subpopulations are distinguished:

Polymorphonuclear MDSC (PMN-MDSC): Morphologically similar to neutrophilic granulocytes; the most abundant subtype.
Monocytic MDSC (M-MDSC): Resemble classical monocytes and are particularly potent suppressors of T-cell activity.

Mechanism of Action

MDSC suppress immune responses through multiple mechanisms:

Production of reactive oxygen species (ROS) and nitric oxide (NO), which damage T cells
Expression of Arginase-1, which depletes L-arginine – an amino acid essential for T-cell function
Secretion of immunosuppressive cytokines such as IL-10 and TGF-β
Induction of regulatory T cells (Tregs), which further dampen immune responses
Inhibition of NK cell activity and antigen-specific immune responses

Clinical Significance

MDSC in Cancer

In oncology, MDSC play a particularly critical role. Tumors release signaling molecules (e.g., G-CSF, GM-CSF, VEGF, IL-6) that block myeloid cell maturation and drive MDSC expansion. MDSC accumulate in the tumor microenvironment and in the blood of cancer patients, where they promote tumor growth, stimulate angiogenesis (formation of new blood vessels), and shield tumors from immune recognition.

MDSC in Infections and Sepsis

During severe infections and sepsis, MDSC also accumulate in large numbers. While they can help dampen excessive inflammatory responses, they may simultaneously impair the ability of the immune system to effectively eliminate pathogens.

MDSC in Autoimmune Diseases

In certain autoimmune conditions, MDSC may paradoxically exert a protective, anti-inflammatory role by moderating the overactive immune response and reducing tissue damage.

Diagnostic Assessment

MDSC are typically identified using flow cytometry based on specific surface marker profiles. Key markers include:

PMN-MDSC: CD11b⁺ CD14^- CD15⁺ CD33⁺ HLA-DR^low/-
M-MDSC: CD11b⁺ CD14⁺ CD15^- HLA-DR^low/-

The precise phenotypic definition of MDSC subsets continues to be refined through international standardization efforts.

Therapeutic Approaches

Targeting MDSC represents a promising strategy in modern cancer immunotherapy. Current approaches include:

Promoting differentiation: Inducing the maturation of MDSC into non-suppressive myeloid cells (e.g., using retinoids such as all-trans retinoic acid, ATRA)
Functional inhibition: Blocking specific suppressive pathways (e.g., Arginase inhibitors, PDE5 inhibitors)
Depletion: Selective elimination of MDSC using antibodies or cytotoxic agents
Combination with immune checkpoint inhibitors: MDSC reduce the efficacy of checkpoint inhibitors (e.g., anti-PD-1/PD-L1); combined strategies may improve therapeutic responses

References

Bronte V et al. – Recommendations for myeloid-derived suppressor cell nomenclature and characterization standards. Nature Communications, 2016;7:12150.
Veglia F, Perego M, Gabrilovich D – Myeloid-derived suppressor cells coming of age. Nature Immunology, 2018;19(2):108–119.
Gabrilovich DI, Nagaraj S – Myeloid-derived suppressor cells as regulators of the immune system. Nature Reviews Immunology, 2009;9(3):162–174.

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