Myeloid-derived suppressor cells (MDSC) are immature myeloid cells that accumulate in the circulation and the tumor microenvironment of most cancer patients. There, MDSC suppress both adaptive and innate immunity, hindering immunotherapies. The inflammatory milieu often present in cancers facilitates MDSC suppressive activity, causing aggressive tumor progression and metastasis. MDSC from tumor-bearing mice release exosomes, which carry biologically active proteins and mediate some of the immunosuppressive functions characteristic of MDSC. Studies on other cell types have shown that exosomes may also carry RNAs which can be transferred to local and distant cells, yet the messenger RNA and microRNA cargo of MDSC-derived exosomes has not been studied to date. Here, the cargo of MDSC and their exosomes was interrogated with the goal of identifying and characterizing molecules that may facilitate MDSC suppressive potency. Because inflammation is an established driving force for MDSC suppressive activity, we used the well-established 4T1 mouse mammary carcinoma system, which includes “conventional” as well as “inflammatory” MDSC. We provide evidence that MDSC-derived exosomes carry proteins, messenger RNAs and microRNAs with different quantitative profiles than that of their parental cells. Several of these molecules have known or predicted functions consistent with MDSC suppressive activity, suggesting a potential mechanistic redundancy.

中文翻译：

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蛋白质，mRNA和miRNA的含量差异表明MDSC及其外泌体可能介导不同的免疫抑制功能

髓样来源的抑制细胞（MDSC）是未成熟的髓样细胞，它们会在大多数癌症患者的循环系统和肿瘤微环境中积聚。在那里，MDSC抑制了适应性免疫和先天免疫，从而阻碍了免疫治疗。癌症中通常存在的炎症环境促进MDSC抑制活性，导致侵袭性肿瘤进展和转移。来自荷瘤小鼠的MDSC释放外泌体，该外泌体携带生物活性蛋白并介导MDSC的某些免疫抑制功能。对其他细胞类型的研究表明，外泌体也可能携带可转移到局部和远处细胞的RNA，但迄今为止，尚未研究过MDSC衍生外泌体的信使RNA和microRNA。这里，为了鉴定和表征可能促进MDSC抑制效力的分子，对MDSC及其外泌体的货物进行了询问。由于炎症是抑制MDSC活性的既定驱动力，因此我们使用了成熟的4T1小鼠乳腺癌系统，该系统包括“常规”和“炎症” MDSC。我们提供的证据表明，MDSC衍生的外来体所携带的蛋白质，信使RNA和微RNA的定量谱与其亲代细胞的定量谱不同。这些分子中的几种具有与MDSC抑制活性一致的已知或预测功能，表明潜在的机械冗余。我们使用了完善的4T1小鼠乳腺癌系统，其中包括“常规”和“炎症” MDSC。我们提供的证据表明，MDSC衍生的外来体所携带的蛋白质，信使RNA和microRNA的定量特征与其亲代细胞的定量特征不同。这些分子中的几种具有与MDSC抑制活性一致的已知或预测功能，表明潜在的机械冗余。我们使用了完善的4T1小鼠乳腺癌系统，其中包括“常规”和“炎症” MDSC。我们提供的证据表明，MDSC衍生的外来体所携带的蛋白质，信使RNA和microRNA的定量特征与其亲代细胞的定量特征不同。这些分子中的几种具有与MDSC抑制活性一致的已知或预测功能，表明潜在的机械冗余。