Transmissible cancers

Came across a paper in Cell published in 2006 about the clonal origin of a transmissible cancer (CTVT) found in dogs. This was the first time I have heard about a tumor cell itself acting as the transmissible agent. The tumor cell itself was shown to be transferred as an allograft came from three different experiments: 1. CTVT can only be experimentally induced by transplanting living tumor cells, and not by lysates or killed cells. 2. The karyotype of the of the tumor cells is aneuploid but striking similar in tumors collected from various regions of unrelated dogs. And 3. A LINE-1 element upstream of c-myc was found in every tumor line examined. This tumor is passed from dog to dog usually by coitus but also can occur from licking and biting. This tumor is not fatal and usually is treatable. This cell has evolved into a parasite which represents the oldest somatic mammalian cell in continuous propagation.

For obvious reasons, Immunologists had a very hard time believing that the transmissible agent was the cell itself. The immune system is built to kill anything that is not recognized as self. So how did this cell evolve in such a way as to evade the hosts immune system? This was one of the questions that this paper sought to answer. As it turns out, MHC class I are downregulated in each of these tumors and class II are absent. Vertebrates has evolved NK cells to detect cells (typically tumors) that do not express MHC I and II and kill them because the normal acquired immune system would not be able to pick up these cells. These CTVT cells seemed to have evolved an expression level of MHC I that is high enough to keep the hosts NK cells at bay but low enough as to not illicit an immune response.

I found this paper really interesting and the authors and myself wonder why this isnt something that has occurred more often. At any rate, its amazing to see evolution in action, even at the cellular level. And we as researchers should look closely at this because it seems not a matter of 'if' but 'when' something like this will be seen in humans.

Murgia, C., Pritchard, JK., Kim, SY., Fassati, A., and Weiss, RA. Clonal Origin and Evolution of Transmissible Cancer. (2006) Cell 126, 477-487