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Hannah Young
Cancer is generally thought to be a disease that develops from one cell that eventually divides and becomes a tumor within an individual; how this cell becomes cancerous differs depending on the initiating event. While some cancers are initiated through a series of mutations in tumor suppressors or oncogenes, some tumors can also be initiated by infection with a virus. An example of this is Human Papillomavirus, which can be spread through sexual contact from one person to another and can cause cervical cancer.
Additionally, cancer can be initiated through the transmission of cancerous cells from one individual to another. Transmissible cancers have only been observed in dogs, mussels, and Tasmanian Devils. Devil Facial Tumor Disease (DFTD) was first identified in Tasmanian Devils in 1996, while a second strain of transmissible cancer was identified in 2014; both have severely damaged Tasmanian Devil populations so much so that the species is now endangered. Several efforts in the last two decades have been made to further understand how the disease is transmitted, its origins, the evolutionary impacts of DFTD on Tasmanian Devil populations, and possible vaccination and treatment strategies for conservation efforts.
DFTD is primarily transmitted from one individual to another through biting of the face, causing facial and oral tumors; cancer cells from the infected individual are then transferred to the uninfected individual. Because initiation of a tumor occurs through transmission of live cancer cells, and not through transmission of a virus that will eventually cause a cell to become cancerous, there was much curiosity about the cell of origin of this transmissible cancer. In 2010, one study found that the cell of origin of DFTD was likely a Schwann cell, a cell type of the nervous system responsible for myelinating nerves. This was discovered by using gene expression profiles of the cancerous cells of DFTD and comparing them to normal cell types.
Many studies have tried to understand how, despite the many mutations in DFT1 and DFT2, the immune system of the Devils is unable to recognize these cancer cells and prevent them from colonizing and developing into a tumor. One probable strategy these cancers use to evade the immune system is dampening the expression of major histocompatibility complex (MHC) molecules, which are essential for detection of malignant or infected cells.Many human cancers also take advantage of the downregulation of MHC molecules to avoid being recognized by the immune system.
Other immune-related mechanisms have been shown to contribute to the susceptibility of Tasmanian Devils to DFTD. T cells are adaptive immune cells that are important for recognizing pathogens and tumors; T cells express T cell receptors (TCRs), which are proteins that recognize small parts of proteins from pathogens or tumors. Having a diverse collection of TCRs can help an organism fight off infection and kill tumors. In 2019, a study was published showing that Tasmanian Devils have a restricted collection of TCRs and after infection with DFTD, this collection becomes even more restricted, suggesting that DFTD has an important impact on the Tasmanian Devil immune system.
Similar to human cancers, immunotherapy is being broadly applied to DFTD in Tasmanian Devils to support conservation efforts. Several studies in the last decade have looked at the immune responses of Tasmanian Devils to DFTD. One study in 2017 found that Tasmanian Devils that were immunized and treated with an immunotherapy after infection with DFTD showed tumor regression in comparison to devils that had not been immunized. The vaccine in this study consisted of DFTD cells that were treated with IFN-ɣ (an immunostimulant) in culture and then administered to the devils. There were several adjuvants used in this study, including stimulants of the innate immune system and ISCOMATRIX™, a saponin-based adjuvant that induces antibody responses. These vaccinations and treatments have proven to be effective in providing some protection against DFTD and will hopefully aid in conservation efforts to preserve the Tasmanian Devil populations.
Edited by MaryAnn Bowyer
Header image: Flickr
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