Tumour-Associated Macrophage Polarisation Promotes Progression of Esophageal Carcinoma

Abstract

<jats:title>Abstract</jats:title> <jats:p><jats:bold>Background:</jats:bold> The immune response mediated by tumour-associated macrophages (TAMs) is vital in tumour progression in many cancers. Fibrinogen-like protein 2 (FGL2) is a critical immunosuppressive factor that regulates the tumour microenvironment. However, no study has yet reported on the relationship between FGL2, tumour-infiltrating lymphocyte recruitment, and prognosis in esophageal carcinoma (ESCA). <jats:bold>Methods: </jats:bold>Differentially expressed genes (DEGs) in various macrophage phenotypes were analysed using the GEO database. We identified the hub genes involved in affecting ESCA clinical prognosis using Kaplan-Meier plotter. Correlations between hub genes and immune infiltrates were analysed using the Tumour Immune Estimation Resource (TIMER) database, while correlation analysis between FGL2 and cytokine expression was assessed using cBioPortal. In vitro cell co-culture experiments were performed to examine the role of FGL2 in promoting tumorigenesis. Finally, we compared the GO terms and KEGG pathways enriched by the DEGs in M1 and M2 macrophages using DAVID.<jats:bold>Results:</jats:bold> High FGL2 expression was significantly associated with poorer overall survival and relapse-free survival of esophageal cancer patients. FGL2 expression was positively correlated with immune markers and infiltrating levels of B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils and dendritic cells. In addition, FGL2 expression was strongly correlated to IL-10, MMP9, CCL5, TIM-3, IL-13, VCAM1, M-CSF and FGF-7 expression. <jats:bold>Conclusions:</jats:bold> M2-like TAMs may regulate the tumour microenvironment by secreting FGL2, thereby inducing the occurrence and progression of ESCA. Reversing TAM polarization may be an effective strategy that reveals new targets for immunotherapy in treating ESCA.</jats:p>