期刊
CELLS
卷 9, 期 6, 页码 -出版社
MDPI
DOI: 10.3390/cells9061561
关键词
CRAMP; antimicrobial peptide; CD73; adenosine; Th17 cells; TGF-beta; p38
类别
资金
- Basic Science Research Program through the National Research Foundation of Korea (NRF) - Ministry of Science, ICT,& Future Planning [NRF-2018R1D1A1B07050262]
- Kangwon National University
The effector function of tumor-infiltrated CD4(+)T cells is readily suppressed by many types of immune regulators in the tumor microenvironment, which is one of the major mechanisms of immune tolerance against cancer. Cathelicidin-related antimicrobial peptide (CRAMP), the mouse analog of LL-37 peptide in humans, is a cationic antimicrobial peptide belonging to the cathelicidin family; however, its secretion by cancer cells and role in the tumor microenvironment (TME) remain unclear. In this study, we explored the possibility of an interaction between effector CD4(+)T cells and CRAMP using in vitro-generated mouse Th17 cells. We found that CRAMP stimulates Th17 cells to express the ectonucleotidase CD73, while simultaneously inducing cell death. This finding suggested that CD73-expressing Th17 cells may function as immune suppressor cells instead of effector cells. In addition, treatment of pharmacological inhibitors of the transforming growth factor-beta (TGF-beta) signaling pathway showed that induction of CD73 expression is mediated by the p38 signaling pathway. Overall, our findings suggest that tumor-derived LL-37 likely functions as an immune suppressor that induces immune tolerance against tumors through shaping effector Th17 cells into suppressor Th17 cells, suggesting a new intervention target to improve cancer immunotherapy.
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