Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.
Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands. Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, the Netherlands.
Cancer Res. 2016 Aug 1;76(15):4332-46. doi: 10.1158/0008-5472.CAN-15-1695. Epub 2016 Jun 20.
The tumor microenvironment is characterized by regulatory T cells, type II macrophages, myeloid-derived suppressor cells, and other immunosuppressive cells that promote malignant progression. Here we report the identification of a novel BDCA1(+)CD14(+) population of immunosuppressive myeloid cells that are expanded in melanoma patients and are present in dendritic cell-based vaccines, where they suppress CD4(+) T cells in an antigen-specific manner. Mechanistic investigations showed that BDCA1(+)CD14(+) cells expressed high levels of the immune checkpoint molecule PD-L1 to hinder T-cell proliferation. While this BDCA1(+)CD14(+) cell population expressed markers of both BDCA1(+) dendritic cells and monocytes, analyses of function, transcriptome, and proteome established their unique nature as exploited by tumors for immune escape. We propose that targeting these cells may improve the efficacy of cancer immunotherapy. Cancer Res; 76(15); 4332-46. ©2016 AACR.
肿瘤微环境的特征是调节性 T 细胞、II 型巨噬细胞、髓系来源的抑制性细胞和其他抑制性细胞，它们促进恶性进展。在这里，我们报告了一种新型 BDCA1(+)CD14(+)免疫抑制性髓系细胞群的鉴定，该细胞群在黑色素瘤患者中扩增，并存在于基于树突状细胞的疫苗中，它们以抗原特异性方式抑制 CD4(+)T 细胞。机制研究表明，BDCA1(+)CD14(+)细胞表达高水平的免疫检查点分子 PD-L1 以阻碍 T 细胞增殖。虽然这个 BDCA1(+)CD14(+)细胞群表达了 BDCA1(+)树突状细胞和单核细胞的标记物，但对其功能、转录组和蛋白质组的分析确立了它们作为肿瘤逃避免疫的独特性质。我们提出，针对这些细胞可能会提高癌症免疫治疗的效果。癌症研究; 76(15); 4332-46。©2016AACR。
