Page 1175 - Veterinary Immunology, 10th Edition

cells suggests that they originate from a clone of myeloid cells that
VetBooks.ir arose in a wolf or East Asian breed of dog about 10,000 years ago.

Devil Facial Tumor Disease

The large carnivorous marsupial, the Tasmanian devil (Sarcophilus

harrissii), is on the brink of extinction as a result of devil facial
tumor disease, a transmissible cancer. This disease first appeared in
1996 and has spread across Tasmania. It has reduced some devil

populations by as much as 90%. Tumor cells are transmitted when
devils bite each other around the face, a common behavior. Animals
die within 3 to 6 months of acquiring the cancer since they are
unable to mount an immune response to the foreign cells. The
tumor cells grow and form a large mass that is eventually lethal

(Fig. 35.8). Almost very devil “infected” with these tumor cells dies
of cancer. Although devils have a functioning immune system, their
limited MHC diversity prevents them from recognizing the tumor

cells as foreign. (The tumor cells originated from Schwann cells
from a female devil in the early-1990s but are continuing to evolve.)
A second, genetically distinct facial tumor lineage (DFT2) has also
been recognized in devils. Facial tumor cells do not express surface
MHC class I due to down-regulation of their β2-microglobulin and

TAP genes. This downregulation is a result of epigenetic
deacetylation of histones. Thus there is no histocompatibility barrier
to tumor growth. Although devils have functioning NK cells these

cannot kill the tumor cells for unknown reasons. MHC expression
can be restored by exposing facial tumor cells to recombinant devil
IFN-γ and subsequent activation of the MHC class II transactivator,
a critical transcription factor. Blood mononuclear cells activated by
mitogens in vitro can also kill devil tumor cells. Encouraging results

have also been obtained by vaccinating animals with killed
adjuvanted tumor cells. It also appears that resistance to this cancer
is emerging in some wild populations.

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