Abstract
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.
Keywords:
FGL2; esophageal carcinoma; immunotherapy; tumour-associated macrophage; tumour-infiltrating.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
B-Lymphocytes
-
CD4-Positive T-Lymphocytes
-
CD8-Positive T-Lymphocytes
-
Cell Line, Tumor
-
Chemokine CCL5 / genetics
-
Chemokine CCL5 / immunology
-
Coculture Techniques
-
Databases, Genetic
-
Dendritic Cells
-
Disease Progression
-
Esophageal Neoplasms / genetics
-
Esophageal Neoplasms / immunology*
-
Esophageal Neoplasms / metabolism
-
Esophageal Neoplasms / pathology
-
Esophageal Squamous Cell Carcinoma / genetics
-
Esophageal Squamous Cell Carcinoma / immunology*
-
Esophageal Squamous Cell Carcinoma / metabolism
-
Esophageal Squamous Cell Carcinoma / pathology
-
Fibrinogen / genetics*
-
Fibroblast Growth Factor 7 / genetics
-
Fibroblast Growth Factor 7 / metabolism
-
Hepatitis A Virus Cellular Receptor 2 / genetics
-
Hepatitis A Virus Cellular Receptor 2 / immunology
-
Humans
-
Interleukin-10 / genetics
-
Interleukin-10 / immunology
-
Interleukin-13 / genetics
-
Interleukin-13 / immunology
-
Lymphocytes, Tumor-Infiltrating / immunology
-
Macrophage Colony-Stimulating Factor / genetics
-
Macrophage Colony-Stimulating Factor / immunology
-
Matrix Metalloproteinase 9 / genetics
-
Matrix Metalloproteinase 9 / metabolism
-
Neutrophils
-
RNA, Messenger
-
THP-1 Cells
-
Tumor Microenvironment
-
Tumor-Associated Macrophages / immunology*
-
Up-Regulation
-
Vascular Cell Adhesion Molecule-1 / genetics
-
Vascular Cell Adhesion Molecule-1 / metabolism
Substances
-
CCL5 protein, human
-
Chemokine CCL5
-
FGF7 protein, human
-
FGL2 protein, human
-
HAVCR2 protein, human
-
Hepatitis A Virus Cellular Receptor 2
-
IL10 protein, human
-
Interleukin-13
-
RNA, Messenger
-
Vascular Cell Adhesion Molecule-1
-
Fibroblast Growth Factor 7
-
Interleukin-10
-
Macrophage Colony-Stimulating Factor
-
Fibrinogen
-
MMP9 protein, human
-
Matrix Metalloproteinase 9