Supplementary Table 3. Differential expression analysis from Class II transactivator induces expression of MHC-I and MHC-II in transmissible Tasmanian devil facial tumours

MHC-I and MHC-II molecules are critical components of antigen presentation and T cell immunity to pathogens and cancer. The two monoclonal transmissible devil facial tumours (DFT1, DFT2) 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. We have previously shown that the overexpression of NLRC5 in DFT1 and DFT2 cells can regulate components of the MHC-I pathway but not MHC-II, establishing the stable upregulation of MHC-I on the cell surface. As MHC-II molecules are crucial for CD4⁺ T cell activation, MHC-II expression in tumour cells is beginning to gain traction in the field of immunotherapy and cancer vaccines. The overexpression of Class II transactivator in transfected DFT1 and DFT2 cells induced the transcription of several genes of the MHC-I and MHC-II pathways. This was further supported by the upregulation of MHC-I protein on DFT1 and DFT2 cells, but interestingly MHC-II protein was upregulated only in DFT1 cells. This new insight into the regulation of MHC-I and MHC-II pathways in cells that naturally overcome allogeneic barriers can inform vaccine, immunotherapy and tissue transplant strategies for human and veterinary medicine.

主要组织相容性复合体I类（MHC-I）与主要组织相容性复合体II类（MHC-II）分子是抗原呈递以及针对病原体与癌症的T细胞免疫的关键组成部分。两种单克隆可传播性袋獾面部肿瘤（DFT1、DFT2）会利用MHC-I通路来规避抗肿瘤免疫与同种异体排斥屏障。该规避机制支撑了DFT细胞在野生袋獾种群中的持续传播。我们此前的研究表明，在DFT1与DFT2细胞中过表达NLRC5可调控MHC-I通路的相关组分，但不影响MHC-II通路，从而使细胞表面的MHC-I实现稳定上调。由于MHC-II分子对于CD4⁺ T细胞活化至关重要，肿瘤细胞中的MHC-II表达目前在免疫治疗与癌症疫苗领域正逐渐受到关注。在转染的DFT1与DFT2细胞中过表达II类反式激活因子（Class II transactivator）可诱导MHC-I与MHC-II通路中多个基因的转录。这一结果进一步得到了DFT1与DFT2细胞表面MHC-I蛋白上调的佐证，但有趣的是，MHC-II蛋白仅在DFT1细胞中实现了上调。这项针对天然可规避同种异体排斥屏障的细胞中MHC-I与MHC-II通路调控机制的新见解，可为人类与兽医学领域的疫苗开发、免疫治疗以及组织移植策略提供参考。