Multifaceted role of myeloid-derived suppressor cells in colorectal cancer

Crosstalk between cancer cells and the immune system is an important determinant of cancer progression. The immune microenvironment of colorectal cancer (CRC) is a complex and heterogeneous system, consisting of massive infiltrations of myeloid cells and lymphocytes that remodel the tumor microenvironment (TME) through the secretion of cytokines, growth factors and proteases to promote or inhibit progression of CRC. Dendritic cells (DCs) and macrophages sense invading microorganisms and regulate the differentiation of inflammatory lymphocytes, further recruiting subsets of myeloid cells into the local intestinal tissue. Of these, Myeloid-derived suppressor cells (MDSCs), one of the most important types of tumor-promoting immune cells, are a diverse population of myeloid cells that strongly suppress antitumor immune responses. Accumulating evidence suggests that MDSCs also play a distinct but crucial role during inflammation-dependent CRC development in patients with inflammatory bowel disease and impede novel CRC immunotherapies. Consequently, MDSCs have emerged as one of the most attractive targets in the antitumor immune axis. This review focuses on the emerging insights into the complex regulatory network of MDSCs in CRC development, and the potential advantages of therapeutic targeting of MDSCs. We summarize the origin, development, differentiation characteristics and known functions of MDSCs. In addition, we describe potential therapeutic strategies based on MDSCs that may have the potential to improve the efficacy of cancer therapies in the future.