Research Paper Volume 13, Issue 2 pp 2049—2072

Tumor-associated macrophage polarization promotes the progression of esophageal carcinoma

Xin Yuan1, , Ya Li1, , An Zhi Zhang1, , Chen Hao Jiang1, , Fan Ping Li1, , Yu Fang Xie1, , Jiang Fen Li1, , Wei Hua Liang1, , Hai Jun Zhang1, , Chun Xia Liu1, , Li Juan Pang1, , Xi Hua Shen1, , Feng Li1,2, , Jian Ming Hu1, ,

  • 1 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
  • 2 Department of Pathology, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China

Received: July 17, 2020       Accepted: October 22, 2020       Published: December 15, 2020
How to Cite

Copyright: © 2020 Yuan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


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 (FGL2), an immunosuppressive factor in the tumor microenvironment of various cancers, was upregulated in M2 macrophages, and higher FGL2 expression was associated with poorer survival in esophageal carcinoma patients. Using the TIMER database, we found that FGL2 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 FGL2 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.


ESCA: esophageal carcinoma; GEO: Gene Expression Omnibus; DEGs: differentially expressed genes; KEGG: Kyoto Encyclopedia of Genes and Genomes; TAMs: Tumor-associated macrophages; FGL2: Fibrinogen-like protein 2.