Myeloid-Derived Suppressor Cells: Therapeutic Target for Gastrointestinal Cancers
Junaid Arshad1, Amith Rao2, Matthew L Repp3
1University of Arizona Cancer Center, GI Medical Oncology, Tucson, AZ 85724, USA.
Abstract:
Gastrointestinal cancers represent one of the more challenging cancers to treat. Current strategies to cure and control gastrointestinal (GI) cancers like surgery, radiation, chemotherapy, and immunotherapy have met with limited success, and research has turned towards further characterizing the tumor microenvironment to develop novel therapeutics. Myeloid-derived suppressor cells (MDSCs) have emerged as crucial drivers of pathogenesis and progression within the tumor microenvironment in GI malignancies. Many MDSCs clinical targets have been defined in preclinical models, that potentially play an integral role in blocking recruitment and expansion, promoting MDSC differentiation into mature myeloid cells, depleting existing MDSCs, altering MDSC metabolic pathways, and directly inhibiting MDSC function. This review article analyzes the role of MDSCs in GI cancers as viable therapeutic targets for gastrointestinal malignancies and reviews the existing clinical trial landscape of recently completed and ongoing clinical studies testing novel therapeutics in GI cancers.
Insights
Myeloid-derived suppressor cells (MDSCs) are key drivers in gastrointestinal cancers. Targeting MDSCs offers a promising new therapeutic strategy for these challenging malignancies.
Area of Science:
- Oncology
- Immunology
- Gastroenterology
Background:
- Gastrointestinal (GI) cancers are difficult to treat with current methods.
- The tumor microenvironment is critical for GI cancer progression.
- Myeloid-derived suppressor cells (MDSCs) significantly impact GI cancer pathogenesis.
Purpose of the Study:
- To analyze the role of MDSCs in GI cancers.
- To identify MDSCs as potential therapeutic targets.
- To review the clinical trial landscape for novel GI cancer therapeutics targeting MDSCs.
Main Methods:
- Literature review of MDSC function in GI cancers.
- Analysis of preclinical models defining MDSC targets.
- Review of completed and ongoing clinical trials for MDSC-targeted therapies.
Main Results:
- MDSCs are crucial drivers of GI cancer progression.
- Multiple strategies exist to target MDSCs, including blocking recruitment, promoting differentiation, depletion, metabolic alteration, and direct function inhibition.
- A growing number of clinical trials are investigating novel MDSC-targeted therapeutics.
Conclusions:
- MDSCs represent a viable and important therapeutic target for GI malignancies.
- Targeting MDSCs holds promise for improving treatment outcomes in GI cancers.
- Further research and clinical trials are essential to fully realize the potential of MDSC-targeted therapies.
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