Interleukin (IL)-27 is a promising anti-cancer cytokine with therapeutic potential. Exhibiting overlapping properties with type I and II interferons (IFNs), IL-27 impacts cancer cell viability and immune cell activity. Known to modulate toll-like receptor (TLR) expression, we investigated whether IL-27 affected TLR-mediated death in cancer cells. Using DU145 and PC3 cell lines as models of prostate cancer, we investigated whether IL-27 and IFN-γ affect TLR3-mediated cell death. Our results demonstrate that when IL-27 or IFN-γ is added with polyinosinic-polycytidylic acid [poly(I:C)], type I IFN (IFN-I) expression increases concurrently with cell death. IL-27 and IFN-γ enhanced TLR3 expression, suggesting a mechanism for sensitization to cell death. Further, PC3 cells were more sensitive to IL-27/poly(I:C)-induced cell death compared with DU145 cells. This correlated with higher production of IFN-β and inducible protein-10 versus IL-6 in response to treatment of PC3 cells compared with DU145. Taken together, this study demonstrates a potential role for IL-27 in the treatment of prostate cancer.
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