Myeloid-derived suppressor cells in colorectal cancer: mechanisms of immunosuppression, therapy resistance and therapeutic targeting.

The overall response of colorectal cancer (CRC) to immune checkpoint blockade remains limited, particularly in patients with microsatellite-stable disease. One important underlying mechanism is the involvement of myeloid-derived suppressor cells (MDSCs) in shaping an immunosuppressive TME. Under the influence of tumor-associated genetic alterations, chronic inflammation, the intestinal microbiota, metabolic stress, and therapeutic pressure, MDSCs undergo aberrant expansion and functional skewing. By remodeling the local immune ecology, they attenuate T cell- and natural killer (NK) cell-mediated antitumor responses. Concurrently, MDSCs are also implicated in angiogenesis, barrier disruption, stromal remodeling, premetastatic niche formation, and therapeutic tolerance. Thus, MDSCs are not only critical mediators of immune evasion but also key components of CRC progression and treatment resistance. Current clinical translation in this field remains constrained by the ambiguous definition of human MDSCs, phenotypic overlap, insufficient functional validation, and imprecise patient stratification. Future studies should integrate single-cell omics, spatial omics, metabolic profiling, and microbiome analyses to establish more functionally oriented biomarkers. On this basis, combination therapeutic strategies targeting MDSC recruitment, suppressive function, or reprogramming states should be further developed.