Myeloid-Derived Suppressor Cells in Cancer

Abstract

Immune evasion is an emerging hallmark of cancer. Many cancersevade the immune system through the overproduction of a wide array of immunosuppressivecells and cytokines, which not only inhibit the host's antitumor immuneresponse, but also hinder the clinical effi cacy of immune-based therapies. Myeloidderivedsuppressor cells (MDSCs) represent a heterogeneous collection of immaturemyeloid cells that play an important role in cancer immune evasion. Theirpresence has been extensively investigated in preclinical models. MDSCs arisefrom myeloid progenitor cells that have failed to terminally differentiate into maturegranulocytes and macrophages and are recruited from the marrow to the tumormicroenvironment through production of various cytokines. One of the major obstaclesin developing clinical strategies targeting MDSCs in cancer patients has beentheir heterogeneity in humans, which thus far has prevented determination of anunambiguous phenotype, shared between mice and humans, that has clinical relevanceand correlates with their suppressive function. In this chapter we review thecurrent clinical literature on MDSCs in cancer patients, showing that there appear tobe two major subsets of MDSCs which are present under different situations. We alsodiscuss the potential use of MDSC as prognostic and predictive markers in cancerpatients. Finally, we examine current strategies designed to modulate MDSCs incancer patients, which represents an innovative and promising approach to enhancethe effectiveness of immune-based therapies.