The transcriptional profile of circulating myeloid derived suppressor cells correlates with tumor development and progression in mouse.,Genes and Immunity

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The transcriptional profile of circulating myeloid derived suppressor cells correlates with tumor development and progression in mouse.
Genes and Immunity ( IF 5.0 ) Pub Date : 2019-03-18 , DOI: 10.1038/s41435-019-0062-3
Ido Nachmany ₁ , Yoel Bogoch ₁ , Gilgi Friedlander-Malik ₂ , Omer Amar ₁ , Ekaterina Bondar ₁ , Nitzan Zohar ₁ , Shay Hantisteanu ₃ , Ofer Fainaru ₄ , Nir Lubezky ₁ , Joseph M Klausner ₁ , Niv Pencovich ₁

Affiliation

Myeloid derived suppressor cells (MDSCs) play key roles in cancer development. Accumulation of peripheral-blood MDSCs (PB-MDSCs) corresponds to the progression of various cancers, but provides only a crude indicator. We aimed toward identifying changes in the transcriptional profile of PB-MDSCs in response to tumor growth. CT26 colon cancer cells and B16 melanoma cells (106) were inoculated into peritoneal cavities of BALB/c mice and subcutaneously to C57-black mice, respectively. The circulating levels and global transcriptional patterns of PB CD11b+Ly6g+ MDSCs were assessed in control mice, and 4, 8, and 11 days following tumor cell inoculation. Although a significant accumulation of PB-MDSCs was demonstrated only 11 days following tumor induction, a pronounced transcriptional response was identified already on day 4 while the tumor was ~1 mm in size. Further transcriptional changes correlated with different stages of tumor growth. Key MDSC genes and canonical signaling pathways were activated along tumor progression. This phenomenon was demonstrated in both cancer models, and a consensus set of 817 genes, involved in myeloid cell recruitment and angiogenesis, was identified. The data suggest that the transcriptional signatures of PB-MDSC may serve as markers for tumor progression, as well as providing potential targets for future therapies.

中文翻译：

循环的髓样来源的抑制细胞的转录谱与小鼠的肿瘤发展和进展有关。

髓样来源的抑制细胞（MDSC）在癌症发展中起关键作用。外周血MDSC（PB-MDSCs）的积累与各种癌症的进展相对应，但仅提供了粗略的指标。我们旨在确定响应肿瘤生长的PB-MDSCs转录谱中的变化。将CT26结肠癌细胞和B16黑色素瘤细胞（106）分别接种到BALB / c小鼠的腹膜腔和C57黑小鼠的皮下。在对照小鼠中，以及肿瘤细胞接种后第4、8和11天，评估了PB CD11b + Ly6g + MDSC的循环水平和整体转录模式。尽管仅在诱导肿瘤后11天就发现了PB-MDSC的大量积累，在第4天，当肿瘤的大小约为1 mm时，已经确定了明显的转录反应。进一步的转录变化与肿瘤生长的不同阶段相关。沿肿瘤进展激活了关键的MDSC基因和规范的信号通路。在两种癌症模型中均证实了这一现象，并确定了涉及髓样细胞募集和血管生成的共有817个基因的共有序列。数据表明，PB-MDSC的转录特征可作为肿瘤进展的标志物，并为将来的治疗提供潜在的靶标。并鉴定了涉及髓细胞募集和血管生成的共有817个基因的共有序列。数据表明，PB-MDSC的转录特征可作为肿瘤进展的标志物，并为将来的治疗提供潜在的靶标。并鉴定了涉及髓细胞募集和血管生成的共有817个基因的共有序列。数据表明，PB-MDSC的转录特征可作为肿瘤进展的标志物，并为将来的治疗提供潜在的靶标。

更新日期：2019-03-18

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