期刊
INTERNATIONAL IMMUNOPHARMACOLOGY
卷 73, 期 -, 页码 118-127出版社
ELSEVIER
DOI: 10.1016/j.intimp.2019.04.058
关键词
Juglone; Myeloid derived suppressor cells (MDSCs); CD8(+) T cells; IL-1 beta
资金
- Natural Science Foundation of China [81572347/81773165]
- Application research and development plan major project of Heilongjiang [GA16C105]
- China Postdoctoral Science Foundation [2015 M581479]
- Natural Science Foundation of Heilongjiang Province for the Returned Overseas Chinese Scholars [LC2016029]
- Yuweihan Academician Outstanding Youth Training Foundation of Harbin Medical University
- Postdoctoral Research Start-up Foundation of Heilongjiang Province [LBH-Q16165]
Myeloid-derived suppressor cells (MDSCs) contribute to immune activity suppression and promote the tumor progression. Elimination of MDSCs is a promising cancer therapeutic strategy, and some chemotherapeutic agents have been reported to hamper tumor progression by suppressing MDSCs. Juglone has been showed to exert a direct cytotoxic effect on tumor cells. However, the effect of juglone on MDSCs and anti-tumor immune statue has remained unexplored. In our study, we observed that juglone suppressed tumor growth and metastasis markedly, and the tumor growth suppression in immunocompetent mice was more drastic than that in immunodeficient mice. Juglone reduced the accumulation of MDSCs and increased IFN-gamma production by CD8(+) T cells. Consistently, juglone affected myeloid cells differentiation and maturation, impairing the immunosuppressive functions of MDSCs. Moreover, juglone down-regulated the level of IL-1 beta which was mediating accumulation of MDSCs. In addition, juglone inhibited 5FU-induced liver injury in a colorectal carcinoma bearing mice model. Thus, our work suggests that the anti-tumor effect of juglone is mediated, at least in part, by eliminating accumulation of MDSCs.
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