Chale Ravinder S, Ghiam Neda, McNamara Stephanie A, Jimenez Joaquin J
Comp Med. 2019 Aug 1;69(4):291-298. doi: 10.30802/AALAS-CM-18-000129. Epub 2019 Aug 6.
Known as devil facial tumor disease (DFTD) and canine transmissible venereal tumor (CTVT), transmissible cancer occurs in both Tasmanian devil and canine populations, respectively. Both malignancies show remarkable ability to be transmitted as allografts into subsequent hosts. How DFTD and CTVT avoid detection by immunocompetent hosts is of particular interest, given that these malignancies are rarely seen in other species in nature. Both of these transmissible cancers can downregulate the host immune system, enabling proliferation. DFTD is characterized by epigenetic modifications to the DNA promoter regions of β₂microglobulin, transporters associated with antigen processing 1 and 2, MHC I, and MHC II-crucial proteins required in the detection and surveillance of foreign material. Downregulation during DFTD may be achieved by altering the activity of histone deacetylases. DFTD has caused widespread destruction of devil populations, placing the species on the brink of extinction. CTVT demonstrates a proliferative phase, during which the tumor evades immune detection, allowing it to proliferate, and a regressive phase when hosts mount an effective immune response. Alteration of TGFβ signaling in CTVT likely impedes the antigen-processing capabilities of canine hosts in addition to hindering the ability of natural killer cells to detect immune system downregulation. Immunosuppressive cytokines such as CXCL7 may contribute to a favorable microenvironment that supports the proliferation of CTVT. When viewed from an evolutionary paradigm, both DFTD and CTVT may conform to a model of host-parasite coevolution. Furthermore, various genetic features, such as genetically active transposons in CTVT and chromosomal rearrangements in DFTD, play important roles in promoting the survival of these disease agents. Understanding the mode of transmission for these transmissible cancers may shed light on mechanisms for human malignancies and reveal opportunities for treatment in the future.
可传播癌症分别发生在袋獾和犬类群体中，被称为袋獾面部肿瘤疾病（DFTD）和犬传染性性病肿瘤（CTVT）。这两种恶性肿瘤都具有作为同种异体移植物传播给后续宿主的显著能力。鉴于这些恶性肿瘤在自然界的其他物种中很少见，DFTD和CTVT如何避免被具有免疫能力的宿主检测到尤其令人感兴趣。这两种可传播癌症都可以下调宿主免疫系统，从而实现增殖。DFTD的特征是对β₂微球蛋白、与抗原加工相关的转运蛋白1和2、MHC I和MHC II（检测和监测外来物质所需的关键蛋白质）的DNA启动子区域进行表观遗传修饰。DFTD期间的下调可能是通过改变组蛋白脱乙酰酶的活性来实现的。DFTD已导致袋獾种群的广泛破坏，使该物种濒临灭绝。CTVT表现出一个增殖期，在此期间肿瘤逃避免疫检测，使其得以增殖，还有一个消退期，此时宿主产生有效的免疫反应。CTVT中TGFβ信号的改变可能除了阻碍自然杀伤细胞检测免疫系统下调的能力外，还会阻碍犬类宿主的抗原加工能力。免疫抑制细胞因子如CXCL7可能有助于形成支持CTVT增殖的有利微环境。从进化范式来看，DFTD和CTVT都可能符合宿主 - 寄生虫共同进化模型。此外，各种遗传特征，如CTVT中的基因活性转座子和DFTD中的染色体重排，在促进这些病原体的生存中发挥着重要作用。了解这些可传播癌症的传播方式可能会揭示人类恶性肿瘤的机制，并为未来的治疗提供机会。
