Targeting Myeloid-Derived Suppressor Cell Trafficking as a Novel Immunotherapeutic Approach in Microsatellite Stable Colorectal Cancer

SIMPLE SUMMARY: Microsatellite stable colorectal cancer represents the majority of patients who have been diagnosed with colorectal cancer, and it is inherently resistant to currently available immunotherapy. After standard-of-care chemotherapy, patients have very limited remaining treatment options. Therefore, defining innovative approaches to reactivate the immune system is critical, and novel treatments are desperately needed. Here, we review and highlight a key immune cell that is involved in reprogramming the immune system in colorectal cancer called the myeloid-derived suppressor cell. The successful targeting of myeloid-derived suppressor cells with novel drug combinations in clinical trials may allow for microsatellite stable colorectal cancer to become responsive to immunotherapy and thereby improve patients’ outcomes. ABSTRACT: Myeloid-derived suppressor cells (MDSCs) are a unique subset of immune cells that promote an immunosuppressive phenotype due to their impacts on CD8 and regulatory T cell function. The inhibition of MDSC trafficking to the tumor microenvironment (TME) may represent a novel target in microsatellite stable (MSS) colorectal cancer with the potential to reprogram the immune system. Here, we review the rationale of inhibiting myeloid suppressor cell trafficking in treatment-refractory MSS colorectal cancer and circulating tumor DNA (ctDNA) positive settings to determine whether this approach can serve as a backbone for promoting immunotherapy response in this difficult-to-treat disease.