The Tasmanian devil, a carnivorous marsupial unique to the island of Tasmania, faces the Devil Facial Tumor Disease (DFTD). This aggressive illness has caused population declines of up to 83% in some local areas, pushing the species toward extinction. Unlike most cancers, DFTD is a transmissible cancer, spreading between individuals when they bite each other, a common behavior during feeding and mating. The cancer cells act like an infectious agent that the host’s body fails to recognize as foreign. Scientists believe that developing a solution lies in understanding and manipulating the devil’s immune system, with a specific focus on the function and activation of T cells.
The Unique Immune Evasion of Devil Facial Tumor Disease
DFTD is one of only a few known contagious cancers, and its success is linked to immune evasion. This strategy involves suppressing Major Histocompatibility Complex (MHC) molecules on the surface of the tumor cells. MHC molecules are normally present on all nucleated cells and function as a display system, presenting internal proteins to the immune system’s T cells.
DFTD cells actively downregulate the genes responsible for producing and transporting MHC Class I molecules. This suppression is a reversible regulatory change, specifically an epigenetic modification. By removing the MHC display system, the tumor cells become “invisible” to the devil’s cytotoxic \(\text{CD8}^{+}\) T cells, which are the primary immune cells responsible for destroying cancerous cells.
This lack of MHC presentation prevents the host’s adaptive immune system from launching a rejection response against the foreign cancer cells. The tumor is able to grow and spread without being targeted by T cell-mediated immunity. This mechanism explains why the disease is so uniformly fatal and why the devil’s immune system does not control the cancer.
T Cell Research: Identifying Immune Targets and Suppression
Research focuses on T cell mechanisms to fight the disease by overcoming MHC downregulation. Treating DFTD cells with the inflammatory molecule interferon-gamma (\(\text{IFN-}\gamma\)) can restore MHC Class I expression on the tumor cell surface. This proves the cancer cells’ antigen presentation machinery is functional and can be reactivated.
\(\text{CD3}^{+}\) T lymphocytes have been observed in rare primary DFTD tumors adjacent to immune clusters. This suggests that when a local immune response is triggered, inflammatory signals, such as \(\text{IFN-}\gamma\), can temporarily force tumor cells to display MHC molecules, making them a T cell target. Studies in mice models show that DFTD cells are immunogenic and can trigger the production of \(\text{IFN-}\gamma\).
Scientists are also investigating T cell suppression mechanisms, such as inhibitory checkpoint molecules. The checkpoint molecule \(\text{PD-L1}\) is upregulated on DFTD cells in response to \(\text{IFN-}\gamma\), which could prevent T cell attack even if MHC expression is restored. Understanding this tumor microenvironment and the T cell profiles of devils that exhibit rare tumor regression provides a blueprint for therapeutic activation.
Translating Immune Knowledge into Conservation Strategies
The insights gained from T cell research are being translated into immunotherapies and prophylactic vaccines. The goal of a DFTD vaccine is to bypass the tumor’s MHC evasion by stimulating a robust T cell response that forces the tumor cells to become visible to the immune system. One promising approach involves using live DFTD cells manipulated to permanently express MHC-I on their surface.
Immunization trials have successfully induced an immune response in devils. This vaccination-primed immunity led to the immune-mediated rejection and regression of established tumors. The objective is to develop a stable, field-deployable vaccine that can be administered to wild populations, possibly through oral bait drops, to provide widespread protection.
Another conservation strategy involves selective breeding programs. Researchers are studying rare devils that exhibit natural resistance or tumor regression to identify genetic markers correlating with a successful anti-DFTD T cell response. By identifying individuals with advantageous Major Histocompatibility Complex alleles or other immune-related genes, conservationists can prioritize them for breeding in captive programs. Releasing these immune-competent individuals into the wild helps increase the frequency of protective immunity within the population.