Journal
IMMUNOLOGY LETTERS
Volume 184, Issue -, Pages 7-14Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.imlet.2017.02.006
Keywords
Interleukin-17; Tumor necrosis factor-alpha; Programmed cell death protein 1 ligand 1; Prostate cancer; Colon cancer
Categories
Funding
- National Institutes of Health [R01CA174714, P20GM103518]
- Department of Defense [W81XWH-14-1-0050, W81XWH-14-1-0149, W81XWH-14-1-0458, W81XWH-15-1-0444]
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Programmed cell death protein 1 (PD-1) acts on PD-1 ligands (PD-L1 and PD-L2) to suppress activation of cytotoxic T lymphocytes. Interleukin-17 (IL-17) and tumor necrosis factor-alpha (TNF-alpha) are co-expressed by T helper 17 (TH17) cells in many tumors. The purpose of this study was to test if IL-17 and TNF-alpha may synergistically induce PD-L1 expression in human prostate cancer LNCaP and human colon cancer HCT116 cell lines. We found that IL-17 did not induce PD-L1 mRNA expression, but up-regulated PD-L1 protein expression in HCT116 and LNCaP cells. TNF-alpha induced PD-L1 mRNA and protein expression in both cell lines. Neither IL-17 nor TNF-alpha induced PD-L2 mRNA or protein expression. IL-17 and TNF-alpha acted individually rather than cooperatively in induction of PD-L1 expression. IL-17 and/or TNF-alpha activated AKT, nuclear factor-kappa B (NF-kappa B), and extracellular signal-regulated kinases 1/2 (ERK1/2) signaling pathways in HCT116 cells, whereas only NF-kappa B signaling was activated in LNCaP cells. NF-kappa B inhibitor could diminish PD-L1 protein expression induced by IL-17 and/or TNF-alpha in both HCT116 and LNCaP cell lines. ERK1/2 inhibitor could also reduce PD-L1 protein expression induced by IL-17 and/or TNF-alpha in HCT116 cells, while AKT inhibitor could abolish PD-L1 protein expression induced by IL-17 and/or TNF-alpha in LNCaP cells. These results suggest that IL-17 and TNF-alpha act individually rather than cooperatively through activation of NF-kappa B and ERK1/2 signaling to up-regulate PD-L1 expression in HCT116 cells, while the two inflammatory cytokines act through activation of NF-kappa B signaling, in the presence of AKT activity, to up-regulate PD-L1 expression in LNCaP cells. (C) 2017 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.
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