Table_1_Myeloid-Derived Suppressor Cells in Immune Microenvironment Promote Progression of Esophagogastric Junction Adenocarcinoma.docx

Adenocarcinoma of the esophagogastric junction (AEG) is a fatal disease. Accumulating evidence indicates that, for a comprehensive understanding of AEG, studies should be conducted not only to investigate tumor cells, but also the tumor microenvironment (TME). In this study, we collected AEG patient data from The Cancer Genome Atlas, and used the CIBERSORT algorithm to analyze tumor-infiltrating immune cell profiles. The levels of CD8+ T cells and M0 and M2 macrophages were relatively high in AEG tissues. M2 macrophages were abundant in G3 tumors, and neutrophils were associated with poor prognosis. Myeloid-derived suppressor cells (MDSCs) represent a heterogeneous population of immunosuppressive cells which share a similar origin to neutrophils and macrophages. We further analyzed the levels of MDSCs in AEG patients and healthy donors (HD) using flow cytometry. MDSC levels were elevated at tumor sites, with polymorphonuclear MDSCs (PMN-MDSCs) being the predominant subtype. Circulating MDSCs partly represented cells at the tumor site. We observed that PMN-MDSC levels at tumor sites were positively correlated with advanced staging, low grade, lymph node metastasis, and HER2− status. Immunohistochemistry and immunofluorescence analyses indicated that activation of the STAT3 and NF-κB pathways in MDSCs may be a potential mechanism for cancer progression. Our studies provided a comprehensive perspective involving tumor-infiltrating immune cells, and detailed insights into the proportion of MDSCs in AEG and their clinical significance. Together, these findings may improve our current understanding of cancer progression involving tumor-infiltrating immune cells in the TME.

食道胃结合部腺癌（AEG）是一种致命性疾病。累积的证据表明，为了对AEG有一个全面的理解，研究不仅应调查肿瘤细胞，还应对肿瘤微环境（TME）进行探究。在本研究中，我们收集了来自癌症基因组图谱的AEG患者数据，并使用CIBERSORT算法分析了肿瘤浸润免疫细胞谱。在AEG组织中，CD8+ T细胞和M0及M2巨噬细胞的水平相对较高。M2巨噬细胞在G3肿瘤中较为丰富，而中性粒细胞与不良预后相关。髓源性抑制细胞（MDSCs）代表了一群异质性的免疫抑制细胞，它们与中性粒细胞和巨噬细胞具有相似的起源。我们进一步利用流式细胞术分析了AEG患者和健康捐赠者（HD）中MDSCs的水平。MDSCs在肿瘤部位的浓度升高，其中多形核MDSCs（PMN-MDSCs）为主要的亚型。循环MDSCs部分代表了肿瘤部位的细胞。我们观察到肿瘤部位的PMN-MDSCs水平与晚期分期、低分级、淋巴结转移和HER2-状态呈正相关。免疫组化和免疫荧光分析表明，MDSCs中STAT3和NF-κB通路的激活可能是癌症进展的潜在机制。我们的研究提供了关于肿瘤浸润免疫细胞的一个全面视角，并对AEG中MDSCs的比例及其临床意义进行了深入探讨。总之，这些发现可能有助于提升我们对肿瘤微环境中肿瘤浸润免疫细胞介导的癌症进展的理解。