The emerging role of myeloid-derived suppressor cells in radiotherapy

Radiotherapy (RT) has been used for decades as one of the main treatment modalities for cancer patients. The therapeutic effect of RT has been primarily ascribed to DNA damage leading to tumor cell death. Besides direct tumoricidal effect, RT affects antitumor responses through immune-mediated mechanism, which provides a rationale for combining RT and immunotherapy for cancer treatment. Thus far, for the combined treatment with RT, numerous studies have focused on the immune checkpoint inhibitors and have shown promising results. However, treatment resistance is still common, and one of the main resistance mechanisms is thought to be due to the immunosuppressive tumor microenvironment where myeloid-derived suppressor cells (MDSCs) play a crucial role. MDSCs are immature myeloid cells with a strong immunosuppressive activity. MDSC frequency is correlated with tumor progression, recurrence, negative clinical outcome, and reduced efficacy of immunotherapy. Therefore, increasing efforts to target MDSCs have been made to overcome the resistance in cancer treatments. In this review, we focus on the role of MDSCs in RT and highlight growing evidence for targeting MDSCs in combination with RT to improve cancer treatment.