Tumor-associated macrophage-derived cytokines enhance cancer stem-like characteristics through epithelial–mesenchymal transition

Yongxu Chen,1,2,* Wei Tan,1 Changjun Wang1,2,* 1Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangdong Geriatric Institute, Guangzhou, Guangdong Province, People’s Republic of China; 2School of Medicine, South China University of Technology, Guangzhou, Guangdong Province, People’s Republic of China *All authors contributed equally to this work Abstract: Cancer stem cells are a small population of cells with the potential for self-renewal and multi-directional differentiation and are an important source of cancer initiation, treatment resistance, and recurrence. Epithelial–mesenchymal transition (EMT) is a process in which epithelial cells lose their epithelial phenotype and convert to mesenchymal cells. Recent studies have shown that cancer cells undergoing EMT can become stem-like cells. Many kinds of tumors are associated with chronic inflammation, which plays a role in tumor progression. Among the various immune cells mediating chronic inflammation, macrophages account for ~30%–50% of the tumor mass. Macrophages are highly infiltrative in the tumor microenvironment and secrete a series of inflammatory factors and cytokines, such as transforming growth factor (TGF)-β, IL-6, IL-10, and tumor necrosis factor (TNF)-α, which promote EMT and enhance the stemness of cancer cells. This review summarizes and discusses recent research findings on some specific mechanisms of tumor-associated macrophage-derived cytokines in EMT and cancer stemness transition, which are emerging targets of cancer treatment. Keywords: macrophage, cancer stem cell, tumor immunology, inflammatory cytokine, tumor microenvironmen