Abstract
BackgroundInterferon regulatory factor 4 (IRF4) is a transcription factor from the IRF factor family that exerts regulatory functions in the immune system and oncogenesis. However, the biological role of IRF4 in colon cancer is still unclear. The aim of this study is to investigate whether IRF4 participates in the immune response in colon cancer.MethodsWe compared the expression of IRF4, the number of regulatory T cells (Tregs) and macrophages in the colon cancer tissues and paracancerous colon tissues from colon cancer patients. Colon cancer mouse model was established by inoculation with colon cancer cells (SW480) as a xenograft tumor, and we observed tumor growth of colon cancer. Furthermore, the mechanism of action of IRF4 in transdifferentiation of Tregs into macrophage-like cells and the effect of IRF4 on colon cancer cells were investigated in vitro.ResultsIRF4 was severely down-regulated in the colon cancer tissues. Colon cancer tissues exhibited an increase in the number of regulatory T cells (Tregs) and macrophages. Furthermore, IRF4 overexpression repressed proliferation, migration and invasion of colon cancer cells (SW480 and HT116 cells). Moreover, IRF4 up-regulation ameliorated tumor growth of colon cancer by promoting the transdifferentiation of Tregs into macrophage-like cells through inhibition of BCL6 expression. Exosomes derived from colon cancer cells repressed IRF4 expression in Tregs by transmitting miR-27a-3p, miR-30a-5p and miR-320c.ConclusionsIRF4 overexpression promoted the transdifferentiation of Tregs into macrophage-like cells to inhibit the occurrence and development of colon cancer. Thus, IRF4 may be a potential target for colon cancer treatment.
Highlights
Interferon regulatory factor 4 (IRF4) is a transcription factor from the IRF factor family that exerts regulatory functions in the immune system and oncogenesis
The data obtained from Quantitative real-time PCR (qRT-PCR) and Western blot (WB) showed that IRF4 was highly expressed in colon cancer tissues with respect to the normal paracancerous colon tissues (Fig. 1a, b)
We found that colon cancer tissues exhibited an increase in the proportions of Tregs and M2 macrophages
Summary
Interferon regulatory factor 4 (IRF4) is a transcription factor from the IRF factor family that exerts regulatory functions in the immune system and oncogenesis. The aim of this study is to investigate whether IRF4 participates in the immune response in colon cancer. Regulatory T cells (Tregs) and tumor associated macrophages (TAMs) are generally considered to be involved in the progression of tumors. Tregs aggregate and migrate into the tumor microenvironment, and suppress the immune response of anti-tumor cytokines. Many studies have shown that the accumulation of Tregs in the tumor microenvironment increases with the development of colon cancer [6, 7]. 80 % of TAMs show anti-inflammatory effects similar to M2 macrophages, but promote the formation of tumor. A small proportion of TAMs show pro-inflammatory effects similar to M1 type macrophages, but inhibits tumor growth [8, 9]. TAMs more exhibit M1 macrophage-like effects may inhibit tumor development
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