Regulation of MHC-I and MHC-II by CIITA in transmissible cancers

MHC-I and MHC-II molecules are critical components of antigen presentation and T cell immunity to pathogens and cancer. The transmissible devil facial tumour (DFT) cells that cause Tasmanian devil facial tumour disease (DFTD) exploit MHC-I pathways to overcome immunological anti-tumour and allogeneic barriers. This exploitation underpins the ongoing transmission of DFT cells across the wild Tasmanian devil population. MHC-II expression is crucial for CD4+ T cell activation and is primarily confined to haematopoietic antigen presenting cells. We discovered that the MHC-II transactivator, CIITA, can induce MHC-II expression in non-haematopoietic cells. Transcriptomic analysis of DFT cell lines revealed that CIITA can upregulate several genes of the MHC-I and MHC-II pathways, resulting in protein expression of MHC-I and MHC-II complexes. The induced expression of MHC-II in transmissible cancers signifies that CIITA can function in non-haematopoietic cancer cells and offer a novel strategy to enhance tumour recognition via MHC-II-restricted tumour antigen presentation. HighlightsO_LINon-haematopoietic devil facial tumour (DFT) cells do not typically express MHC-II C_LIO_LICIITA regulates components of the MHC-I and MHC-II machinery in DFT cells C_LIO_LICIITA can induce MHC-I and MHC-II expression in DFT1 cells C_LIO_LISerum from devils with tumour regressions binds to DFT cells that express CIITA C_LIO_LIMHC-II expression in transmissible cancers has implications for anti-tumour immunity C_LI