Contagious cancer: Lessons from the devil and the dog

Abstract

Cancer is generally defined as uncontrollable growth of cells caused by genetic aberrations and/or environmental factors. Yet contagious cancers also occur. The recent emergence of a contagious cancer in Tasmanian devils has reignited interest in transmissible cancers. Two naturally occurring transmissible cancers are known: devil facial tumour disease and canine transmissible venereal tumour. Both cancers evolved once and have then been transmitted from one individual to another as clonal cell lines. The dog cancer is ancient; having evolved more than 6,000 years ago, while the devil disease was first seen in 1996. In this review I will compare and contrast the two diseases focusing on the life histories of the clonal cell lines, their evolutionary trajectories and the mechanisms by which they have achieved immune tolerance. A greater understanding of these contagious cancers will provide unique insights into the role of the immune system in shaping tumour evolution and may uncover novel approaches for treating human cancer.

Immunology of a Transmissible Cancer Spreading among Tasmanian Devils

“…CTVT does not metastasize and does not usually cause the death of the host (11). There are many excellent articles on CTVT (12)(13)(14) and reviews comparing CTVT and DFTD (15,16). This review concentrates on DFTD.…”

Studying immunity to zoonotic diseases in the natural host — keeping it real

“…Finally, studies of Tasmanian devil facial tumour disease and canine transmissible venereal tumour have helped us to understand the role of the immune system in shaping tumour evolution and have provided insights into the crucial roles of MHC genes (reviewed in REF. 27).…”

Oncogenesis as a Selective Force: Adaptive Evolution in the Face of a Transmissible Cancer

“…The emergence of DFTD has been attributed to the low level of genetic diversity at the non‐self‐recognising Major Histocompatibility Complex (MHC) immune genes . However, the recent spread of DFTD to areas with genetically disparate devil populations has revealed that DFTD successfully crosses histocompatibility barriers that would normally prevent allograft acceptance demonstrating that devil MHC polymorphism does not affect tumour cell transmission .…”

“…The emergence of DFTD has been attributed to the low level of genetic diversity at the non-self-recognising Major Histocompatibility Complex (MHC) immune genes. [85] However, the recent spread of DFTD to areas with genetically disparate devil populations has revealed that DFTD successfully crosses histocompatibility barriers that would normally prevent allograft acceptance demonstrating that devil MHC polymorphism does not affect tumour cell transmission. [86] Rather, DFTD is actively evading the host immune system by down-regulating genes involved in the antigen-processing pathways, resulting in the concomitant loss of cell surface expression of MHC Class I molecules, and escape of immune recognition.…”