Myeloid-Derived Suppressor Cells in Cancer: Metabolic Reprogramming, Immune Crosstalk, and Therapeutic Targeting

Area of Science:

• Immunology
• Cancer Biology
• Metabolic Regulation

Background:

• Myeloid-derived suppressor cells (MDSCs) are key regulators of tumor-associated immunosuppression.
• MDSCs promote tumor progression, angiogenesis, metastasis, and immunotherapy resistance.
• Two main subsets, PMN-MDSCs and Mo-MDSCs, exhibit distinct characteristics.

Purpose of the Study:

• To review the heterogeneity, metabolic adaptations, and immune interactions of MDSCs in cancer.
• To discuss therapeutic strategies targeting MDSC functions.
• To highlight the role of MDSC metabolism in shaping the tumor microenvironment (TME).

Main Methods:

• Literature review of MDSC biology in cancer.
• Analysis of MDSC phenotypic and functional heterogeneity.
• Examination of metabolic pathways and immune cell crosstalk.

Main Results:

• MDSCs orchestrate immune escape through complex interactions within the TME.
• Metabolic rewiring, including glycolysis and ROS production, sustains MDSC suppressive activity.
• MDSC-NK cell crosstalk impairs anti-tumor immunity.

Conclusions:

• Understanding MDSC heterogeneity and metabolism is crucial for cancer therapy.
• Targeting MDSC recruitment, differentiation, or metabolic pathways may overcome immunosuppression.
• Novel therapeutic strategies can improve the efficacy of cancer immunotherapies.