Human cancer cells respond to cytosolic nucleic acids via RIG-I-MAVS-IRF3-mediated interferon-β production

Abstract

Abstract The innate immune system is the first line of defense against invading microbes via the action of pattern recognition receptors (PRR). Recently, human cancer cells were reported to express PRRs and respond to cytosolic nucleic acids by producing type I interferon. However, whether all nucleic acid-sensing pathways are intact and whether these pathways function in all types of cancer cells remain unclear. In this study, we investigated the effects of nucleic acids in eight types of cancer cells transfected with 5′ppp-dsRNA, poly(A:U), poly(I:C)-HMW, poly(I:C)-LMW, ISD, HSV60, VACV-70, poly(dG:dC), 3′-3′cGAMP, and poly(dA:dT). Interferon-β (IFN-β) secretion was increased following stimulation with 5′ppp-dsRNA, poly(I:C)-HMW, poly(I:C)-LMW, or poly(dA:dT) in most cells. Further, we evaluated the role of TLR3 and RIG-I/MDA-5 signaling in the pancreatic cancer cell line PANC-1. The expression of RIG-I, MDA5, and LGP2 was up-regulated by cytosolic poly(I:C) and poly(dA:dT). Knockdown experiments confirmed that IFN-β production was mediated by the RIG-I-IPS-1-IRF3 signaling pathway in response to cytosolic poly(I:C) and poly(dA:dT). Therefore, these potent adjuvant activities may be useful for drug and vaccine design for cancer immunotherapy.