RNA-sequencing of DFT cell lines treated with interferon-gamma (IFNG) or overexpressing NLRC5

Downregulation of major histocompatibility complex I (MHC-I) on tumor cells is a primary means of immune evasion by many types of cancer. Additionally, MHC-I proteins are a primary target of humoral and cellular mechanisms associated with transplant rejection. Transmissible tumors that overcome mechanisms of allograft rejection and evade anti-tumor immunity have killed thousands of wild Tasmanian devils (Sarcophilus harrisii). Interferon-gamma (IFN?) upregulates surface MHC-I expression on devil facial tumor (DFT) cells but is not sufficient to induce tumor regressions. Transcriptome analysis of IFN?-treated DFT cells revealed strong upregulation of NLR caspase recruitment domain containing protein 5 (NLRC5), a master regulator of MHC-I in humans and mice. To explore the role of NLRC5 in transmissible cancers, we developed DFT cell lines that constitutively overexpress NLRC5. Transcriptomic results suggest that the role of NLRC5 as a master regulator of MHC-I is conserved in devils, and that expression of NLRC5 can drive expression of many components of the antigen presentation pathway.