Department of Pathology and Key Laboratory for Xinjiang Endemic and Ethnic Diseases (Ministry of Education), Department of Pathology, The First Affiliated Hospital, Shihezi University School of Medicine, Xinjiang 832000, China.
Department of Pathology, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China.
Aging (Albany NY). 2020 Dec 15;13(2):2049-2072. doi: 10.18632/aging.202201.
The immune response facilitated by tumor-associated macrophages is a vital determinant of tumor progression. We identified differentially expressed genes between various macrophage phenotypes in the Gene Expression Omnibus, and used Kaplan-Meier Plotter to determine which of them altered the prognosis of esophageal carcinoma patients. Fibrinogen-like protein 2 (), an immunosuppressive factor in the tumor microenvironment of various cancers, was upregulated in M2 macrophages, and higher expression was associated with poorer survival in esophageal carcinoma patients. Using the TIMER database, we found that expression correlated positively with the levels of immune markers of infiltrating B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils and dendritic cells in esophageal carcinoma samples. Correlation analyses in cBioPortal revealed that the mRNA levels of correlated strongly with those of interleukin 10, matrix metalloproteinase 9, C-C motif chemokine ligand 5, T-cell immunoglobulin mucin 3, interleukin 13, vascular cell adhesion molecule 1, macrophage colony-stimulating factor and fibroblast growth factor 7 in esophageal carcinoma tissues. The same cytokines were upregulated when esophageal squamous cell carcinoma cells were co-cultured with M2-like tumor-associated macrophages. Thus, by secreting FGL2, M2-like tumor-associated macrophages may create an immunosuppressive tumor microenvironment that induces the occurrence and progression of esophageal carcinoma.
肿瘤相关巨噬细胞促进的免疫反应是肿瘤进展的重要决定因素。我们在基因表达综合数据库中鉴定了不同巨噬细胞表型之间差异表达的基因，并使用 Kaplan-Meier Plotter 确定了哪些基因改变了食管癌患者的预后。纤维蛋白原样蛋白 2()是各种癌症肿瘤微环境中的一种免疫抑制因子，在 M2 巨噬细胞中上调，其表达水平较高与食管癌患者的生存预后较差相关。使用 TIMER 数据库，我们发现在食管癌样本中，表达与浸润 B 细胞、CD8+T 细胞、CD4+T 细胞、巨噬细胞、中性粒细胞和树突状细胞的免疫标志物水平呈正相关。cBioPortal 的相关性分析显示，在食管癌组织中，mRNA 水平与白细胞介素 10、基质金属蛋白酶 9、C-C 基序趋化因子配体 5、T 细胞免疫球蛋白粘蛋白 3、白细胞介素 13、血管细胞黏附分子 1、巨噬细胞集落刺激因子和碱性成纤维细胞生长因子 7 的水平密切相关。当食管鳞状细胞癌细胞与 M2 样肿瘤相关巨噬细胞共培养时，这些相同的细胞因子也被上调。因此，M2 样肿瘤相关巨噬细胞通过分泌 FGL2 可能会产生一种免疫抑制的肿瘤微环境，从而诱导食管癌的发生和进展。
