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.