Myeloid-Derived Suppressor Cells (MDSCs) in Cancer: Understanding Immune Suppression and New Therapeutic Opportunities

 

Myeloid-Derived Suppressor Cells in Cancer: New Frontiers in Cancer Immunotherapy

Introduction

Cancer progression is influenced not only by malignant cells but also by the complex biological environment surrounding them. Immune cells, stromal cells, blood vessels, signaling molecules, and metabolic factors interact within the tumor microenvironment (TME) and can shape tumor growth and treatment response.

Among these components, myeloid-derived suppressor cells (MDSCs) have attracted increasing attention in cancer research. MDSCs are a heterogeneous group of myeloid cells that can accumulate during chronic inflammation and cancer and suppress important antitumor immune functions. They can interfere with T cells and natural killer (NK) cells and contribute to immune escape, tumor progression, metastasis, and resistance to some cancer treatments.

The growing understanding of MDSC biology has opened new research directions in cancer immunology. Scientists are investigating how these cells develop, how they communicate with cancer and immune cells, how their activity can be measured, and whether targeting MDSCs can improve the effectiveness of existing cancer therapies.

As precision oncology increasingly considers the biological characteristics of both tumors and their surrounding microenvironment, MDSCs represent an important area of investigation for next-generation cancer treatment strategies.

 

What Are Myeloid-Derived Suppressor Cells?

Myeloid-derived suppressor cells are a heterogeneous population of myeloid cells with immunosuppressive properties. They can expand under conditions associated with cancer and chronic inflammation.

Under normal physiological conditions, myeloid cells develop through regulated processes of hematopoiesis and differentiate into mature immune-cell populations. In cancer, persistent inflammatory signals and tumor-derived factors can disrupt normal myeloid differentiation and promote the expansion and accumulation of suppressive myeloid populations.

MDSCs can be found in:

• Peripheral blood
• Bone marrow
• Lymphoid organs
• Primary tumor tissues
• Metastatic sites

Their presence and activity can vary according to cancer type, disease stage, treatment status, and individual patient biology.

Importantly, MDSCs are not a single uniform cell population. Their heterogeneity is one of the major challenges in studying and therapeutically targeting them.

 

Major Types of MDSCs

MDSCs are commonly divided into two major populations based on their phenotype and biological characteristics.

Polymorphonuclear MDSCs

Polymorphonuclear MDSCs (PMN-MDSCs) share some characteristics with neutrophils and are sometimes referred to as granulocytic MDSCs.

They can accumulate in tumors and peripheral blood and contribute to immune suppression through mechanisms involving reactive oxygen species, metabolic regulation, and other suppressive pathways.

Monocytic MDSCs

Monocytic MDSCs (M-MDSCs) have characteristics related to monocytes and can develop into macrophage-like or dendritic-cell-like populations under particular conditions.

They can suppress T-cell responses and contribute to the immunosuppressive environment surrounding tumors.

Although this classification is useful, current research recognizes that MDSC populations can be highly heterogeneous and may change their characteristics depending on the tumor environment.

 

How Do MDSCs Develop in Cancer?

Cancer cells can release cytokines, chemokines, growth factors, and other signaling molecules that influence myeloid-cell development.

Chronic inflammation can alter normal myelopoiesis and promote the accumulation of immature or suppressive myeloid populations.

Several tumor-associated conditions can contribute to MDSC development and activity, including:

• Chronic inflammation
• Hypoxia
• Nutrient deprivation
• Metabolic stress
• Tumor-derived cytokines
• Chemokine signaling
• Endoplasmic-reticulum stress
• Abnormal growth-factor signaling

These factors can create an environment in which MDSCs survive and maintain immunosuppressive functions.

 

MDSCs in the Tumor Microenvironment

Once recruited into tumor tissues, MDSCs interact with cancer cells, T cells, NK cells, dendritic cells, macrophages, endothelial cells, fibroblasts, and other components of the TME.

These interactions can establish a feedback loop:

Tumor signals → MDSC recruitment and expansion → immune suppression → tumor immune escape → further tumor progression

MDSCs therefore represent an important connection between inflammation, immune regulation, and tumor biology.

Recent research has also highlighted the ability of MDSCs to adapt their transcriptional and metabolic programs according to local environmental conditions.

How MDSCs Suppress Antitumor Immunity

One of the most important characteristics of MDSCs is their ability to interfere with immune-cell activity.

Suppression of T Cells

MDSCs can suppress T-cell activation and function through several mechanisms.

These include:

• Depletion of essential amino acids
• Production of reactive oxygen species
• Nitric oxide-related signaling
• Alteration of antigen-specific immune responses
• Release of immunosuppressive mediators
• Direct interactions with immune cells

By limiting effective T-cell activity, MDSCs can weaken the immune system's ability to recognize and attack cancer cells.

Effects on Natural Killer Cells

Natural killer cells are important components of innate antitumor immunity.

MDSCs can suppress NK-cell activity and reduce their ability to contribute to effective tumor-cell elimination.

Effects on Other Immune Cells

MDSCs can also interact with:

• Dendritic cells
• B cells
• Regulatory T cells
• Macrophages
• Other myeloid populations

These interactions can further influence the balance between immune activation and immune suppression within tumors.

 

MDSCs and Cancer Immune Escape

Cancer cells can avoid immune destruction through multiple mechanisms.

MDSCs contribute to this process by creating an immunosuppressive environment that reduces the effectiveness of immune surveillance.

Instead of acting against malignant cells, immune cells within the tumor may become functionally impaired or redirected toward states that support tumor persistence.

This makes MDSCs an important research target in understanding cancer immune escape.

 

MDSCs and Tumor Progression

MDSCs can influence tumor biology through both immune and non-immune mechanisms.

Their activity has been associated with processes such as:

• Tumor growth
• Angiogenesis
• Tissue remodeling
• Invasion
• Metastasis
• Immune suppression
• Formation of supportive metastatic environments

Research indicates that MDSCs can participate in complex interactions that extend beyond direct immune suppression.

 

MDSCs and Cancer Metastasis

Metastasis requires cancer cells to survive, migrate, enter circulation, establish distant sites, and adapt to new tissues.

MDSCs may influence several stages of this process.

They can contribute to the development of microenvironments that support tumor-cell survival and may participate in the formation of conditions favorable to metastatic colonization.

Research is also investigating how MDSCs interact with circulating tumor cells and distant tissues during metastatic progression.

 

MDSCs and Angiogenesis

Tumor growth requires the development and remodeling of blood-vessel networks.

MDSCs can participate in angiogenic processes by producing or influencing signaling factors that affect endothelial cells and the tumor vasculature.

This can contribute to the formation of a tumor environment that supports continued growth.

The relationship between MDSCs, angiogenesis, and hypoxia is an important area of ongoing research.

 

MDSCs and Immunotherapy Resistance

The development of immune checkpoint inhibitors has transformed treatment for several cancers. However, not all patients respond, and some tumors develop resistance.

MDSCs are increasingly being studied as one component of the immunosuppressive environment associated with resistance to cancer immunotherapy.

Their ability to inhibit T-cell and NK-cell activity can create conditions in which immune-based therapies have reduced effectiveness.

This has encouraged researchers to investigate whether targeting MDSCs alongside immunotherapy can improve treatment responses.

 

MDSCs as Potential Cancer Biomarkers

MDSCs are also being investigated as potential biomarkers.

Researchers are examining whether:

• MDSC levels in blood
• MDSC density within tumors
• Specific MDSC phenotypes
• Functional activity
• Changes during treatment

could provide information about disease progression or treatment response.

However, reliable clinical application requires standardized definitions, robust measurement methods, and validation across patient populations.

The heterogeneity of MDSCs remains an important challenge for biomarker development.

 

How Are MDSCs Identified?

MDSC identification can involve combinations of:

• Flow cytometry
• Immunohistochemistry
• Immunofluorescence
• Mass cytometry
• Single-cell RNA sequencing
• Transcriptomic analysis
• Spatial profiling

Because MDSCs share characteristics with other myeloid populations, identifying them accurately can be challenging.

Researchers therefore increasingly use combinations of phenotypic markers and functional measurements rather than relying on a single marker.

Standardization of MDSC identification is particularly important when comparing research findings across studies and clinical trials.

 

Single-Cell Technologies and MDSC Research

Single-cell technologies are helping researchers investigate the diversity of myeloid populations within tumors.

Single-cell RNA sequencing (scRNA-seq) can reveal differences in gene-expression programs between individual cells and help identify distinct myeloid states.

This can provide information about:

• MDSC differentiation
• Cellular heterogeneity
• Signaling pathways
• Metabolic programs
• Interactions with neighboring cells
• Changes during treatment

Recent research has specifically highlighted the potential of single-cell approaches to refine understanding of MDSC developmental states and functional diversity.

 

Spatial Biology and MDSCs

Knowing where an immune cell is located within a tumor can provide additional information beyond its molecular profile.

Spatial technologies can help researchers determine whether MDSCs are concentrated near:

• Tumor-cell regions
• Blood vessels
• Necrotic areas
• Hypoxic regions
• Immune-cell clusters
• Invasive tumor margins

Combining spatial information with molecular profiling could help researchers understand how MDSCs interact with other components of the tumor microenvironment.

This may become increasingly important for developing biomarker-guided cancer therapies.

 

MDSCs and Cancer Metabolism

Tumors often contain abnormal metabolic conditions, including limited nutrients, low oxygen levels, and altered metabolite concentrations.

MDSCs can adapt to these conditions through metabolic changes.

Their metabolic activity may influence:

• T-cell function
• Nutrient availability
• Oxidative stress
• Tumor-cell interactions
• Immune suppression

Recent research has emphasized metabolic reprogramming as an important component of MDSC plasticity and function within the tumor microenvironment.

 

Therapeutic Strategies Targeting MDSCs

Researchers are investigating several approaches to target MDSCs.

These strategies can broadly be divided into four categories:

1. Reducing MDSC expansion
2. Blocking MDSC recruitment
3. Inhibiting MDSC suppressive functions
4. Promoting differentiation into less suppressive mature myeloid cells

Direct depletion of selected MDSC populations is another area of investigation.

 

1. Blocking MDSC Recruitment

Tumors use chemokine and cytokine signaling to recruit myeloid cells.

Blocking selected recruitment pathways may reduce the accumulation of MDSCs in tumor tissues.

This strategy aims to prevent the tumor from building a strong immunosuppressive myeloid environment.

However, chemokine networks are complex, and blocking one pathway may not always be sufficient because tumors can use alternative signaling mechanisms.

 

2. Reducing MDSC Expansion

Another strategy involves interfering with the signals responsible for MDSC development and expansion.

Researchers are studying pathways associated with:

• Growth factors
• Cytokines
• Transcription factors
• Inflammatory signaling
• Myeloid-cell differentiation

The goal is to reduce the generation of suppressive myeloid cells without disrupting normal immune-cell production.

 

3. Inhibiting MDSC Function

Instead of removing MDSCs, researchers can attempt to prevent them from suppressing immune responses.

Potential approaches include interfering with:

• Arginase activity
• Reactive oxygen species
• Nitric oxide pathways
• Immunosuppressive signaling
• Metabolic pathways

This strategy could preserve the cells while reducing their tumor-supportive functions.

 

4. Promoting MDSC Differentiation

Another approach is to encourage MDSCs to differentiate into mature myeloid cells with less suppressive activity.

This concept is based on the observation that abnormal myeloid differentiation contributes to MDSC accumulation.

Promoting normal differentiation could therefore potentially reduce immunosuppression without requiring complete elimination of myeloid cells.

 

MDSC Targeting and Immune Checkpoint Inhibitors

Combining MDSC-targeted strategies with immune checkpoint inhibitors is an important area of research.

The basic concept is:

MDSC targeting → reduced immune suppression → improved immune-cell activity → enhanced potential for checkpoint blockade

However, clinical translation remains challenging.

MDSCs are heterogeneous, their levels can change during treatment, and the most effective combination may vary according to tumor type and patient biology.

Current research therefore emphasizes better patient selection and identification of tumors in which suppressive myeloid cells are major drivers of treatment resistance.

 

MDSCs and Chemotherapy

Chemotherapy can influence the immune microenvironment in multiple ways.

Depending on the drug, treatment schedule, tumor type, and patient characteristics, chemotherapy may alter MDSC numbers and function.

Researchers are therefore investigating whether combining chemotherapy with MDSC-directed approaches could improve antitumor responses.

This area requires careful study because treatments that modify the immune environment can have different effects depending on biological context.

 

MDSCs and Radiotherapy

Radiotherapy can cause tumor-cell damage and alter inflammatory signaling.

These changes may influence the recruitment and activity of myeloid cells.

Consequently, MDSC modulation is being explored as a potential component of combination strategies involving radiation.

Understanding the timing of radiation and MDSC-targeted treatment may be particularly important for future therapeutic development.

 

MDSCs and Other Myeloid Cells

MDSCs do not function independently.

They interact with macrophages, dendritic cells, monocytes, neutrophils, and other myeloid populations.

Some MDSC populations may also undergo differentiation or functional transitions within the tumor environment.

This creates a complex network of myeloid-cell interactions that can influence tumor immunity and treatment response.

 

Artificial Intelligence in MDSC Research

Artificial intelligence and computational biology are increasingly being incorporated into cancer research.

Potential applications include:

• Automated analysis of tissue images
• Identification of immune-cell populations
• Spatial mapping of MDSCs
• Analysis of single-cell datasets
• Prediction of immune-cell interactions
• Integration of clinical and molecular data
• Identification of potential biomarkers

AI-based approaches could help researchers analyze large datasets and identify patterns that may not be easily detected using conventional approaches.

However, computational findings still require biological and clinical validation.

 

MDSCs and Precision Oncology

Precision oncology has traditionally focused heavily on genetic alterations within cancer cells.

The growing understanding of the tumor immune environment suggests that precision treatment may eventually incorporate additional layers of biological information.

MDSC profiling could potentially help researchers investigate:

• Immune-suppressive tumor phenotypes
• Treatment resistance
• Immunotherapy response
• Tumor progression
• Potential combination strategies
• Changes in the immune environment during treatment

This could contribute to a broader model of precision oncology in which both tumor-cell biology and immune-microenvironment biology are considered.

 

Challenges in MDSC Research

Despite substantial progress, several challenges remain.

MDSC Heterogeneity

MDSCs are not a single uniform cell type. Their phenotype and function can differ between tumors and patients.

Identification Challenges

MDSCs can share markers with other myeloid populations, making accurate identification difficult.

Lack of Universal Biomarkers

A standardized biomarker that reliably identifies all clinically relevant MDSCs has not yet been established.

Tumor-Specific Biology

MDSC biology can vary considerably across cancer types.

Treatment Complexity

MDSC-targeted approaches may need to be combined with other therapies to achieve meaningful antitumor effects.

Clinical Translation

Promising findings from laboratory and animal models do not always translate directly into successful clinical treatments. Recent reviews emphasize the need for better patient selection, treatment combinations, and context-specific understanding of tumor myeloid cells.

 

The Future of MDSC-Targeted Cancer Therapy

The future of MDSC research is likely to focus on increasingly precise characterization of these cells.

Instead of simply measuring the total number of MDSCs, researchers may increasingly investigate:

• MDSC subtype
• Functional state
• Spatial location
• Metabolic profile
• Gene-expression program
• Interaction with other immune cells
• Changes during therapy

The combination of single-cell sequencing, spatial biology, proteomics, metabolomics, digital pathology, and artificial intelligence may provide a more detailed picture of MDSC biology.

Another important direction is the development of rational combination therapies.

Rather than targeting MDSCs alone, future approaches may combine MDSC modulation with immune checkpoint inhibitors, targeted therapies, chemotherapy, radiotherapy, or other immunotherapeutic strategies.

Recent 2026 research continues to emphasize MDSCs as potential predictive and prognostic biomarkers while highlighting the need for more precise therapeutic strategies and better clinical translation.

 

Conclusion

Myeloid-derived suppressor cells have become an important focus of cancer immunology because of their ability to regulate immune responses within the tumor microenvironment.

By suppressing T-cell and NK-cell activity, interacting with other immune populations, influencing angiogenesis and metastasis, and contributing to treatment resistance, MDSCs can participate in several biological processes associated with cancer progression.

At the same time, MDSC biology is highly complex. Their heterogeneity, plasticity, and similarity to other myeloid populations make accurate identification and therapeutic targeting challenging.

Advances in single-cell sequencing, spatial profiling, computational biology, and precision medicine are helping researchers move toward a more detailed understanding of MDSCs.

Future cancer treatment strategies may increasingly combine MDSC characterization, biomarker-guided patient selection, and targeted immune modulation with established cancer therapies.

As research continues, MDSCs may provide important insights into how tumors manipulate the immune system and how the tumor microenvironment can be therapeutically reshaped.

 

Join WCOCC-2026

The World Conference on Oncology & Cancer Care (WCOCC-2026) brings together oncologists, cancer researchers, clinicians, scientists, healthcare professionals, academics, and industry experts to exchange knowledge on emerging developments in oncology and cancer care.

Researchers working in cancer immunology, MDSC biology, tumor immunology, immunotherapy, tumor microenvironment, precision oncology, cancer biomarkers, translational oncology, and related fields are invited to share their research and scientific perspectives.

World Conference on Oncology & Cancer Care (WCOCC-2026)

November 19–21, 2026
Tokyo, Japan

Researchers and healthcare professionals are invited to submit their abstracts and participate in scientific discussions focused on emerging developments in cancer research and treatment.

Frequently Asked Questions

1. What are myeloid-derived suppressor cells?

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of myeloid cells with immunosuppressive functions that can accumulate during cancer and chronic inflammation.

2. What is the role of MDSCs in cancer?

MDSCs can suppress antitumor immune responses and contribute to tumor progression, immune escape, angiogenesis, metastasis, and resistance to some cancer therapies.

3. What are the main types of MDSCs?

The two commonly recognized populations are polymorphonuclear MDSCs (PMN-MDSCs) and monocytic MDSCs (M-MDSCs).

4. How do MDSCs suppress T cells?

MDSCs can use several mechanisms, including amino-acid depletion, reactive oxygen species, nitric-oxide-related pathways, and other immunosuppressive mechanisms to reduce T-cell activity.

5. Do MDSCs affect NK cells?

Yes. MDSCs can suppress NK-cell activity and contribute to a tumor environment in which innate antitumor immunity is weakened.

6. Can MDSCs contribute to immunotherapy resistance?

Research indicates that MDSCs can contribute to resistance to cancer immunotherapies by creating immunosuppressive conditions that interfere with effective immune responses.

7. Can MDSCs be targeted in cancer treatment?

Researchers are investigating approaches that reduce MDSC expansion, block their recruitment, inhibit their suppressive functions, promote their differentiation, or selectively deplete suppressive populations.

8. Can MDSC-targeted therapy be combined with immunotherapy?

Yes. Combining MDSC-targeted strategies with immune checkpoint inhibitors and other treatments is an active area of research. The optimal combinations and patient populations remain important questions for clinical investigation.

9. Can MDSCs serve as cancer biomarkers?

MDSC levels and characteristics are being investigated as potential predictive or prognostic biomarkers. However, their heterogeneity and challenges in standardized identification need to be addressed before broad clinical application.

10. How are MDSCs studied?

Researchers use techniques including flow cytometry, immunohistochemistry, immunofluorescence, single-cell sequencing, spatial profiling, transcriptomics, and other molecular approaches to characterize MDSCs.

11. What is the future of MDSC research?

Future research is likely to focus on more precise MDSC classification, spatial and single-cell analysis, biomarker development, metabolic profiling, targeted modulation, and rational combination therapies.