%0 Journal Article
%T IL-36β promotes anti-tumor effects in CD8+ T cells by downregulating micro-RNA let-7c-5p.
%A Li D
%A Huang Y
%A Yu Z
%A Zhang J
%A Hu C
%A Bai Y
%A Wang J
%A Zhang Z
%A Ouyang J
%A Zhou J
%A Zhao X
%J Ann Transl Med
%V 9
%N 23
%D Dec 2021
%M 35071428
%F 3.616
%R 10.21037/atm-21-5991
%X <B>BACKGROUND: </B>The anti-tumor effect of interleukin (IL)-36β-mediated activation of CD8+ T cells has been reported, but the molecular mechanism is largely undefined.<BR><B>METHODS: </B>The levels of IL-36β in pancreatic cancer were examined by quantitative real-time PCR (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. We then examined the changes of CD8+ T cells and natural killer (NK) cells in the tumor by flow cytometry. The microRNA expression profiles were determined by microarray analysis.<BR><B>RESULTS: </B>The results revealed decreased levels of IL-36β in pancreatic cancer tissues. In addition, IL-36β inhibited tumor growth and promoted CD8+ T and NK cell proliferation in the tumor microenvironment (TME). Moreover, IL-36β stimulated CD8+ T cells to synthesize high amounts of interferon-gamma (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 effect. Further experiments demonstrated that IL-36β downregulated IFN-γ in let-7c-5p+ CD8+ T cells.<BR><B>CONCLUSIONS: </B>These findings suggest IL-36β promotes IFN-γ and IL-2 production in CD8+ T cells, as well as anti-tumor effects in CD8+ T cells by downregulating let-7c-5p.