Immunology of naturally transmissible tumours

Abstract

Naturally transmissible tumours can emerge when a tumour cell gains the ability to pass as an infectious allograft between individuals. The ability of these tumours to colonize a new host and to cross histocompatibility barriers contradicts our understanding of the vertebrate immune response to allografts. Two naturally occurring contagious cancers are currently active in the animal kingdom, canine transmissible venereal tumour (CTVT), which spreads among dogs, and devil facial tumour disease (DFTD), among Tasmanian devils. CTVT are generally not fatal as a tumour-specific host immune response controls or clears the tumours after transmission and a period of growth. In contrast, the growth of DFTD tumours is not controlled by the Tasmanian devil's immune system and the disease causes close to 100% mortality, severely impacting the devil population. To avoid the immune response of the host both DFTD and CTVT use a variety of immune escape strategies that have similarities to many single organism tumours, including MHC loss and the expression of immunosuppressive cytokines. However, both tumours appear to have a complex interaction with the immune system of their respective host, which has evolved over the relatively long life of these tumours. The Tasmanian devil is struggling to survive with the burden of this disease and it is only with an understanding of how DFTD passes between individuals that a vaccine might be developed. Further, an understanding of how these tumours achieve natural transmissibility should provide insights into general mechanisms of immune escape that emerge during tumour evolution.

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.…”

Cancer in the parasitic protozoans Trypanosoma brucei and Toxoplasma gondii

“…This disease has been ascertained to have originated as a single cancer cell clone from a single animal ∼11,000 y ago (19,20) and seems to be relatively benign, in that it does not cause death of the dog. Both of the diseases DFTD and CTVT, although different in their respective pathogenicity, are caused by cancer cells that behave as allografts (21), but have developed the ability to escape from surveillance and destruction by the host immunity (22). This avoidance may occur by epigenetic down-regulation of cell surface MHC receptors (23).…”

A Sixth Modality of Infectious Disease: Contagious Cancer from Devils to Clams and Beyond

“…The Major Histocompatibility Complex (MHC) genes in jawed vertebrates form a very strong (but not insurmountable) barrier to cancer allografts. Indeed, CTVT is known to down-regulate expression of MHC genes [31] and carries multiple mutations in genes involved in self-antigen presentation and apoptosis [32]. It has been suggested that lack of MHC diversity in devils contributes to the lack of host recognition of DFTD cells [33,34], but despite their low diversity, experimental allogeneic skin transplants in devils were recognized and rejected [35], and it has recently been shown that DFTD also down-regulates expression of MHC genes [36].…”