The Nature of Myeloid-Derived Suppressor Cells in the Tumor Microenvironment

Myeloid-derived suppressor cells (MDSC) are one of the major components of the tumor microenvironment. The main feature of these cells is their potent immune suppressive activity. MDSC are generated in the bone marrow and, in tumor-bearing hosts, migrate to peripheral lymphoid organs and the tumor to contribute to the formation of the tumor microenvironment. Recent findings have revealed differences in the function and fate of MDSC in the tumor and peripheral lymphoid organs. We review these findings here and, in this context, we discuss the current understanding as to the nature of these differences, the underlying mechanisms, and their potential impact on the regulation of tumor progression.

TrendsIn tumor-bearing hosts, MDSC are generated in the bone marrow and migrate to peripheral lymphoid organs and tumor tissues. This process is controlled by a set of defined chemokines, many of which are upregulated in cancer.In peripheral lymphoid organs, M-MDSC differentiate to macrophages and dendritic cells. By contrast, in the tumor site, M-MDSC have an altered differentiation pattern, rapidly differentiating to tumor-associated macrophages.The nature of tumor MDSC suppression is different from that of MDSC in peripheral lymphoid organs. As a result, both PMN-MDSC and M-MDSC in the tumor site have more potent suppressive activity than their counterparts in peripheral lymphoid organs. In contrast to MDSC in peripheral lymphoid organs, tumor MDSC suppress T cells in an antigen nonspecific manner.Hypoxia appears to have a critical role in the regulation of MDSC differentiation and function in tumors.