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.

肿瘤进展与由多种组分构成的免疫抑制性微环境密切相关，这类微环境包含调节性T细胞（regulatory T cells）、2型巨噬细胞以及髓系来源抑制细胞（myeloid-derived suppressor cells）等多种成分。本研究首次鉴定出一类BDCA1+CD14+免疫抑制细胞群，该细胞群同时存在于黑色素瘤患者的血液与肿瘤组织中。我们证实，在基于树突状细胞（dendritic cell, DC）的抗肿瘤疫苗中，这类细胞的存在会以抗原特异性方式显著抑制CD4+ T细胞。为揭示该抑制活性的作用机制，我们发现BDCA1+CD14+细胞高表达免疫检查点分子PD-L1，从而阻碍T细胞增殖。值得注意的是，尽管这类具有免疫抑制功能的BDCA1+CD14+细胞群同时表达BDCA1+树突状细胞与单核细胞的标志物，但功能、转录组与蛋白质组学分析均明确显示，它们是一类独特的细胞群，可被肿瘤利用以逃避免疫监视。因此，靶向这类细胞或可提升癌症免疫治疗的疗效。