Targeting myeloid regulatory cells in cancer by chemotherapeutic agents

Recent findings in humans and numerous experimental models provide evidence of the important role of immune regulatory cells in cancer and various diseases. "Myeloid regulatory cells" (MRC) include myeloid-derived suppressor cells, regulatory dendritic cells, regulatory macrophages, and subsets of granulocytes that expand during pathologic conditions and that have the ability to suppress cellular immunity. A decrease in MRC population and/or activity has been shown to have positive immune-potentiating effects. Several clinical trials have thus been initiated with the goal of manipulating the expansion or activation of these cells and thereby improving patient immune responses. New data from our own and other laboratories recently revealed that ultralow noncytotoxic doses of certain chemotherapeutic drugs could up-regulate antitumor immunity by modulating the formation, differentiation, and/or function of MRC. This new phenomenon, termed "chemomodulation," allows for the regulation of the tumor microenvironment without the undesirable toxic effects associated with conventional chemotherapy. However, further studies are required before this new targeted therapy can find its way to patients with cancer.