A novel tumor-associated myeloid cell population inhibits antigen-specific immune responses in cancer patients. Homo sapiens

Tumor progression is associated with an immunosuppressive microenvironment that consists of several elements, such as regulatory T cells, type 2 macrophages and myeloid-derived suppressor cells. Here, we identify for the first time a BDCA1+CD14+ population of immunosuppressive cells that resides both in the blood and tumor of melanoma patients. We demonstrated that the presence of these cells in dendritic cell (DC)-based anti-tumor vaccines significantly suppresses CD4+ T cells in an antigen-specific manner. In an attempt to reveal the mechanism of this suppressive activity, we noticed that BDCA1+CD14+ cells express elevated levels of the check-point molecule PD-L1, which thereby hinders T cell proliferation. Importantly, although this suppressive BDCA1+CD14+ population expresses markers of both BDCA1+ DCs and monocytes, functional, transcriptome and proteome analyses clearly revealed that they comprise a unique population of cells that is exploited by tumors to evade immunity. Thus, targeting these cells may improve the efficacy of cancer immunotherapy. Overall design: mRNA profiles of BDCA1+ DCs, BDCA1+CD14+ cells and monocytes, isolated from 3 healthy volunteers, were generated by deep RNA sequencing using HiSeq 2000 System (TruSeq SBS KIT-HS V3，Illumina)