Myeloid-derived suppressor cells (MDSCs) promote immunosuppressive activities in the tumor microenvironment (TME), resulting in increased tumor burden and diminishing the anti-tumor response of immunotherapies. While primary and metastatic tumors are typically the focal points of therapeutic development, the immune cells of the TME are differentially programmed by the tissue of the metastatic site. In particular, MDSCs are programmed uniquely within different organs in the context of tumor progression. Given that MDSC plasticity is shaped by the surrounding environment, the proteomes of MDSCs from different metastatic sites are hypothesized to be unique. A bottom-up proteomics approach using sequential window acquisition of all theoretical mass spectra (SWATH-MS) was used to quantify the proteome of CD11b⁺ cells derived from murine liver metastases (LM) and lung metastases (LuM). A comparative proteomics workflow was employed to compare MDSC proteins from LuM (LuM-MDSC) and LM (LM-MDSC) while also elucidating common signaling pathways, protein function, and possible drug-protein interactions. SWATH-MS identified 2516 proteins from 200 µg of sample. Of the 2516 proteins, 2367 have matching transcriptomic data. Upregulated proteins from lung and liver-derived murine CD11b⁺ cells with matching mRNA transcriptomic data were categorized based on target knowledge and level of drug development. Comparative proteomic analysis demonstrates that liver and lung tumor-derived MDSCs have distinct proteomes that may be subject to pharmacologic manipulation.

髓源性抑制细胞 (MDSCs) 促进肿瘤微环境 (TME) 中的免疫抑制活性，导致肿瘤负荷增加并减弱免疫疗法的抗肿瘤反应。虽然原发性和转移性肿瘤通常是治疗发展的焦点，但 TME 的免疫细胞由转移部位的组织进行不同的编程。特别是，在肿瘤进展的背景下，MDSCs 在不同器官内被独特地编程。鉴于 MDSC 的可塑性受周围环境的影响，来自不同转移部位的 MDSC 的蛋白质组被假设是独一无二的。自下而上的蛋白质组学方法使用所有理论质谱的顺序窗口采集 (SWATH-MS) 来量化 CD11b ⁺的蛋白质组源自鼠肝转移 (LM) 和肺转移 (LuM) 的细胞。采用比较蛋白质组学工作流程来比较来自 LuM (LuM-MDSC) 和 LM (LM-MDSC) 的 MDSC 蛋白质，同时还阐明了常见的信号通路、蛋白质功能和可能的药物-蛋白质相互作用。SWATH-MS 从 200 µg 样品中鉴定了 2516 种蛋白质。在 2516 种蛋白质中，2367 种具有匹配的转录组数据。根据靶点知识和药物开发水平，对来自肺和肝源性小鼠 CD11b ⁺细胞的具有匹配 mRNA 转录组数据的上调蛋白进行分类。比较蛋白质组学分析表明，肝和肺肿瘤衍生的 MDSC 具有不同的蛋白质组，可能会受到药理学操作的影响。