Around 40% of humans and Tasmanian devils (Sarcophilus harrisii) develop cancer in their lifetime, compared to less than 10% for most species. In addition, devils are affected by two of the three known transmissible cancers in mammals. Immune checkpoint immunotherapy has transformed human medicine, but a lack of species-specific reagents has limited checkpoint immunology in most species. We developed a cut-and-paste reagent development system and used the fluorescent fusion protein system to show that immune checkpoint interactions are conserved across 160,000,000 years of evolution, CD200 is highly expressed on transmissible tumor cells, and coexpression of CD200R1 can block CD200 surface expression. The system’s versatility across species was demonstrated by fusing a fluorescent reporter to a camelid-derived nanobody that binds human programmed death ligand 1. The evolutionarily conserved pathways suggest that naturally occurring cancers in devils and other species can be used to advance our understanding of cancer and immunological tolerance.

大约 40% 的人类和塔斯马尼亚恶魔（Sarcophilus harrisii) 在其一生中患上癌症，而大多数物种的发病率不到 10%。此外，魔鬼受到哺乳动物中三种已知的传染性癌症中的两种的影响。免疫检查点免疫疗法已经改变了人类医学，但缺乏物种特异性试剂限制了大多数物种的检查点免疫学。我们开发了一种剪切粘贴试剂开发系统，并使用荧光融合蛋白系统表明免疫检查点相互作用在 160,000,000 年的进化中是保守的，CD200 在可传播的肿瘤细胞上高度表达，并且 CD200R1 的共表达可以阻断 CD200 表面表达. 该系统在物种间的多功能性通过将荧光报告基因融合到与人类程序性死亡配体 1 结合的骆驼衍生的纳米体上得到证明。