Myeloid-derived suppressor cells (MDSCs) are innate immune cells that acquire the capacity to suppress adaptive immune responses during cancer. It remains elusive how MDSCs differ from their normal myeloid counterparts, which limits our ability to specifically detect and therapeutically target MDSCs during cancer. Here, we sought to determine the molecular features of breast cancer-associated MDSCs using the widely studied mouse model based on the mouse mammary tumor virus (MMTV) promoter-driven expression of the polyomavirus middle T oncoprotein (MMTV-PyMT). To identify MDSCs in an unbiased manner, we used single-cell RNA sequencing to compare MDSC-containing splenic myeloid cells from breast tumor-bearing mice with wild-type controls. Our computational analysis of 14,646 single-cell transcriptomes revealed that MDSCs emerge through an aberrant neutrophil maturation trajectory in the spleen that confers them an immunosuppressive cell state. We establish the MDSC-specific gene signature and identify CD84 as a surface marker for improved detection and enrichment of MDSCs in breast cancers.

中文翻译：

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使用单细胞转录组学定义乳腺癌中髓源性抑制细胞的出现。

髓源性抑制细胞 (MDSC) 是先天免疫细胞，在癌症期间获得抑制适应性免疫反应的能力。仍然不清楚 MDSCs 与正常骨髓对应物有何不同，这限制了我们在癌症期间特异性检测和治疗靶向 MDSCs 的能力。在这里，我们试图使用基于小鼠乳腺肿瘤病毒 (MMTV) 启动子驱动的多瘤病毒中间 T 癌蛋白 (MMTV-PyMT) 表达的广泛研究的小鼠模型来确定乳腺癌相关 MDSC 的分子特征。为了以公正的方式识别 MDSC，我们使用单细胞 RNA 测序来比较来自荷瘤小鼠和野生型对照的含有 MDSC 的脾髓细胞。我们对 14 的计算分析，646 个单细胞转录组显示，MDSCs 通过脾脏中异常的中性粒细胞成熟轨迹出现，赋予它们免疫抑制细胞状态。我们建立了 MDSC 特异性基因特征，并将 CD84 鉴定为表面标记，以改进乳腺癌中 MDSC 的检测和富集。