Myeloid-Derived Suppressor Cells in Cancer

Abstract

Immune evasion is an emerging hallmark of cancer. Many cancers evade the immune system through the overproduction of a wide array of immunosuppressive cells and cytokines, which not only inhibit the host’s antitumor immune response, but also hinder the clinical efficacy of immune-based therapies. Myeloid-derived suppressor cells (MDSCs) represent a heterogeneous collection of immature myeloid cells that play an important role in cancer immune evasion. Their presence has been extensively investigated in preclinical models. MDSCs arise from myeloid progenitor cells that have failed to terminally differentiate into mature granulocytes and macrophages and are recruited from the marrow to the tumor microenvironment through production of various cytokines. One of the major obstacles in developing clinical strategies targeting MDSCs in cancer patients has been their heterogeneity in humans, which thus far has prevented determination of an unambiguous phenotype, shared between mice and humans, that has clinical relevance and correlates with their suppressive function. In this chapter we review the current clinical literature on MDSCs in cancer patients, showing that there appear to be two major subsets of MDSCs which are present under different situations. We also discuss the potential use of MDSC as prognostic and predictive markers in cancer patients. Finally, we examine current strategies designed to modulate MDSCs in cancer patients, which represents an innovative and promising approach to enhance the effectiveness of immune-based therapies.