IL-27 Enhances the Expression of TRAIL and TLR3 in Human Melanomas and Inhibits Their Tumor Growth in Cooperation with a TLR3 Agonist Poly(I:C) Partly in a TRAIL-Dependent Manner
PLoS ONE, ISSN: 1932-6203, Vol: 8, Issue: 10, Page: e76159
2013
- 31Citations
- 29Captures
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Metrics Details
- Citations31
- Citation Indexes31
- 31
- CrossRef13
- Captures29
- Readers29
- 29
Article Description
Interleukin (IL)-27 is a member of the IL-6/IL-12 cytokine family and possesses potent antitumor activity, which is mediated by multiple mechanisms. Toll-like receptor (TLR)3 is the critical sensor of the innate immune system that serves to identify viral double-stranded RNA. TLR3 is frequently expressed by various types of malignant cells, and recent studies reported that a synthetic TLR3 agonist, polyinosinic-polycytidylic acid [poly(I:C)], induces antitumor effects on malignant cells. In the present study, we have explored the effect of IL-27 on human melanomas and uncovered a previously unknown mechanism. We found that IL-27 inhibits in vitro tumor growth of human melanomas and greatly enhances the expression of TNF-related apoptosis inducing ligand (TRAIL) in a dose-dependent manner. Neutralizing antibody against TRAIL partly but significantly blocked the IL-27-mediated inhibition of tumor growth. In addition, IL-27 and poly(I:C) cooperatively augmented TRAIL expression and inhibited tumor growth. The cooperative effect could be ascribed to the augmented expression of TLR3, but not retinoic acid-inducible gene-I or anti-melanoma differentiation-associated gene 5, by IL-27. The inhibition of tumor growth by the combination was also significantly abrogated by anti-TRAIL neutralizing antibody. Moreover, IL-27 and poly(I:C) cooperatively suppressed in vivo tumor growth of human melanoma in immunodeficient mice. Taken together, these results suggest that IL-27 enhances the expression of TRAIL and TLR3 in human melanomas and inhibits their tumor growth in cooperation with poly(I:C), partly in a TRAIL-dependent manner. Thus, IL-27 and the combination of IL-27 and poly(I:C) may be attractive candidates for cancer immunotherapy. © 2013 Chiba et al.
Bibliographic Details
10.1371/journal.pone.0076159; 10.1371/journal.pone.0076159.g005; 10.1371/journal.pone.0076159.g004; 10.1371/journal.pone.0076159.g003; 10.1371/journal.pone.0076159.g002; 10.1371/journal.pone.0076159.g001; 10.1371/journal.pone.0076159.g006
http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84885416680&origin=inward; http://dx.doi.org/10.1371/journal.pone.0076159; http://www.ncbi.nlm.nih.gov/pubmed/24155891; https://dx.plos.org/10.1371/journal.pone.0076159.g005; http://dx.doi.org/10.1371/journal.pone.0076159.g005; https://dx.plos.org/10.1371/journal.pone.0076159.g004; http://dx.doi.org/10.1371/journal.pone.0076159.g004; https://dx.plos.org/10.1371/journal.pone.0076159.g003; http://dx.doi.org/10.1371/journal.pone.0076159.g003; https://dx.plos.org/10.1371/journal.pone.0076159.g002; http://dx.doi.org/10.1371/journal.pone.0076159.g002; https://dx.plos.org/10.1371/journal.pone.0076159.g001; http://dx.doi.org/10.1371/journal.pone.0076159.g001; https://dx.plos.org/10.1371/journal.pone.0076159.g006; http://dx.doi.org/10.1371/journal.pone.0076159.g006; https://dx.plos.org/10.1371/journal.pone.0076159; https://dx.doi.org/10.1371/journal.pone.0076159.g005; https://journals.plos.org/plosone/article/figure?id=10.1371/journal.pone.0076159.g005; https://dx.doi.org/10.1371/journal.pone.0076159; https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0076159; https://dx.doi.org/10.1371/journal.pone.0076159.g001; https://journals.plos.org/plosone/article/figure?id=10.1371/journal.pone.0076159.g001; https://dx.doi.org/10.1371/journal.pone.0076159.g003; https://journals.plos.org/plosone/article/figure?id=10.1371/journal.pone.0076159.g003; https://dx.doi.org/10.1371/journal.pone.0076159.g002; https://journals.plos.org/plosone/article/figure?id=10.1371/journal.pone.0076159.g002; https://dx.doi.org/10.1371/journal.pone.0076159.g004; https://journals.plos.org/plosone/article/figure?id=10.1371/journal.pone.0076159.g004; https://dx.doi.org/10.1371/journal.pone.0076159.g006; https://journals.plos.org/plosone/article/figure?id=10.1371/journal.pone.0076159.g006; http://dx.plos.org/10.1371/journal.pone.0076159; https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0076159&type=printable; http://dx.plos.org/10.1371/journal.pone.0076159.g001; http://dx.plos.org/10.1371/journal.pone.0076159.g005; http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0076159; http://dx.plos.org/10.1371/journal.pone.0076159.g006; http://dx.plos.org/10.1371/journal.pone.0076159.g003; http://dx.plos.org/10.1371/journal.pone.0076159.g004; http://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0076159; http://dx.plos.org/10.1371/journal.pone.0076159.g002; http://www.plosone.org/article/metrics/info:doi/10.1371/journal.pone.0076159; http://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0076159&type=printable
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