IL-36β Promotes Anti-Tumor Effects in CD8+ T Cells by Downregulating Micro-RNA Let-7c-5p

Abstract

\n Background: The anti-tumor effect of IL-36β mediated activation of CD8+ T cells has been reported, but the molecular mechanism is largely undefined.Methods: IL-36β amounts in pancreatic cancer were examined by qRT-PCR and immunohistochemical staining. Cytology and animal experiments were performed to study the effects of IL-36β on the growth of pancreatic cancer cells. Then we examined the changes of CD8+ T cells and NK cells in the tumor flow-cytometrically. MicroRNA expression profiles were determined by microarray analysis.Results: The results revealed decreased IL-36β amounts in pancreatic cancer tissues. In addition, IL-36β inhibited tumor growth and promoted CD8+ T and NK cell proliferation in the tumor microenvironment. Moreover, IL-36β stimulated CD8+ T cells to synthesize high amounts of IFN-γ and IL-2. Microarray analysis showed that IL-36β administration to human and mouse CD8+ T cells consistently downregulated the miRNA let-7c-5p. Downregulation of let-7c-5p resulted in IFN-γ and IL-2 upregulation in CD8+ T Cells, whereas its upregulation had the opposite effects. Further experiments demonstrated that IL-36β downregulated IFN-γ in let-7c-5p+ CD8+ T cells. Conclusion: These findings suggest IL-36β promotes IFN-γ and IL-2 production in CD8+ T cells, and IL-36β promotes anti-tumor effects in CD8+ T cells by downregulating micro-RNA let-7c-5p.