Gastrointestinal stromal tumors regulate macrophage M2 polarization through the MIF/CXCR4 axis to immune escape
Shuomeng Xiao, Rui Xu, Yingxin Yang, Rui Zhao, Yuan Xie, Xu-dan Lei, Xiaoting Wu
Abstract
Purpose The infiltration of immune cells and their roles of the infiltrating-immune cells in gastrointestinal stromal tumor (GIST) is still unclear. We aimed to discover the infiltration cell types and the relationship between the infiltrating-immune cells and the progression of GIST. Experimental design Single-cell RNA sequencing were performed to discover types of the infiltrating-immune cells and to analyze CellChat between cells. Immunohistochemistry of 80 GIST samples were used to clarify the relation between macrophages and recurrence risk. In vitro , flow cytometry and Real-time PCR were performed to uncover a potential mechanism of tumor cell regulation of macrophages. Results Tumor cells, macrophages, and T-cells were the predominant cell types. The MIF/CXCR4 axis was the most common ligand–receptor interaction between macrophages and tumor cells. As the risk increased, expression levels of CD68, CD206, MIF, and CXCR4 gradually increased. In vitro , we found that GIST882 was able to secrete MIF and GIST882 cell supernatant upregulated M2 polarization. Real-time PCR showed that expression levels of IL-10 mRNA and Arginase-1 mRNA were also the highest in the GIST882 cell supernatant group. Conclusions These findings identify that macrophages are the most abundant infiltrating cells in GIST. The MIF/CXCR4 axis is the most common ligand–receptor interaction between macrophages and tumor cells. GIST cells can regulate macrophage M2 polarization through the MIF/CXCR4 axis.