Myeloid-derived suppressor cell-dependent inhibition of B cell responses in non-small cell lung cancer

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of cells with potent immune suppression activities. These cells are derived from the bone marrow (BM) and consist of two populations: polymorphonuclear MDSCs (PMN-MDSCs) and monocytic MDSCs (M-MDSCs), morphologically similar to neutrophils and monocytes, respectively. In mice, PMN-MDSCs are recognized as CD11b+Ly6ClowLy6G+, whereas M-MDSCs are CD11b+Ly6ChighLy6G？. In contrast, in humans, CD11b+CD14？CD15+CD33+ cells with low density are defined as PMN-MDSCs, while CD11b+CD14+CD15？CD33+HLA？DR？/low are markers for M-MDSCs (1). Accumulation of MDSCs is often dependent on persistent inflammation in the tumor microenvironment (TME) which provides signals for their expansion and pathological activation. Upon activation, MDSCs gain increased capacity to generate reactive oxygen species (ROS) and nitric oxide (NO), express high levels of arginase and PD-L1, and secrete a variety of tumor-promoting inflammatory factors, including IL-10, TGF-β and PGE2 (1). Under the influence of the TME, MDSCs fail to differentiate into mature myeloid cells, such as mature neutrophils, macrophages and dendritic cells (DCs) that could promote antitumor immune activities. Instead, MDSCs function as potent immune suppressors, diverting specific immune responses on multiple fronts (1)