Myeloid-derived suppressor cells in tumor-induced T cell suppression and tolerance

Tumor development is often associated with a deep alteration of normal myelopoiesis, leading to a progressive accumulation of various cellular elements, belonging to myelomonocytic lineage, in the tumor bed, in the blood, and in both primary and secondary lymphoid organs. This heterogeneous pool of cells expresses, in the mouse, the common markers CD11b and Gr-1 (Ly6C/G) and is endowed with the ability to suppress antigen and/or polyclonal-driven T cell immune response. These cells, named myeloid-derived suppressor cells (MDSCs), are mobilized from hematopoietic organs by cytokines and other factors produced by the tumors, as well as by strong activation of the immune system, and have a profound influence on the outcome of the T cell-dependent immune responses. MDSCs can restrain T cell function directly in an antigen-independent manner; however, in vivo, MDSCs can also process and present tumor-associated antigen and can lead to T cell tolerance in an antigen-specific manner. Furthermore, MDSCs seem to be key players in tumor-induced suppressive network that includes T regulatory (Treg) cells, inhibitory natural killer T (NKT) cells, mast cells, Th17, as well as effector T cells. The importance of MDSCs in human malignancies has been demonstrated in recent years and new approaches targeting their suppressive/tolerogenic action are currently being tested in both preclinical model and clinical trials.