Devil Facial Tumor Disease
Kacy O'Brien
Cell Biology
Morehead State University
Introduction
- A transimissible cancer that is affecting Tasmanian Devil populations - passed by biting.
- DFTD has landed Tasmanian Devils on the International Union for the Conservation of Nature' s endangered species list.
- This type of tumor transmission is seen in one other vertebrate disease.
Origin
Origin
- Cancer cells do not have regulated division and are sometimes unaffected by the immune system.
- The tumors are clonally transmitted from one individual to another.
- Affects individuals over the majority of the geographic distribution.
Pathology
- Tumors are local to the facial area - mostly inside the mouth and on the head.
- sizes of tumors are >3cm.
- the tumors are often broken and bacterially infected.
- The tumors metastasize in lymph nodes, lungs, and kidneys and can cause organ failure.
- The cancer cells contain a pseudocapsule.
- Cells are not consistent in size or shape.
Fatality
- Starvation or organ failure.
Key players
- Lack of epithelial markers, epithelial membrane antigens, and von Wilebrand factors - sarcoma classification.
- Express proteins associated with the peripheral nervous system and are positive for Schwann cell marker periaxin - Schwann cell origin.
The Allograft Theory
- Karyotyping of 11 tumor cells revealed a complex chromosomal arrangement and that was identical in each tumor cell.
- The abnormalities in the chromosomes were identical in each.
- This arrangement was not by chance - indicates that each tumor is a clone that came from one original tumor.
The Allograft Theory
Microsatellite and MHC tests:
Tests
- Genotyping at multiple loci for multiple individuals with different genotypes showed identical in tumor cells at the multiple loci - this proved true independent of age, sex, and location of host.
Transmission
Transmission
Three possible routes of establishment of the clonal tumor:
1. The immune response in the individual is not stong enough.
2. All the individuals have identical major histocompatibility complex.
3. The tumor cells developed mechanisms to escape the immune response of individuals.
The Immune Response
The Immune Respose
- Tasmanian Devils actually have a well-developed immune system similar to other mammals.
- There immune system shows efficiency of neutrophils.
- Experiments have proven a quick response of immunoglobin antibodies against foreign cells - including a secondary memory response.
- All current knowlege shows that the immune respomses are functioning normally (i.e. mitogen-induced responses and cytotoxic responses)
Varying genes of the MHC
MHC
- The Major Histocompatibility complex consists of genes dealing with foreign tissue transplants, and pathogen/tumor detecting mechanisms of the immune system.
- Create T-cell responses to fight against incompatible cells.
- The polymorphic nature of the MHC causes more disease resistence because more antigen fragments can be produced.
- Due to Tasmanian devils having a small range and being an endemic species with not much gene flow their genetic diversity is low including at the MHC location.
- A skin grafting experiment showed rejction of foreign MHC by tasmanian devils - meaning there was enough diversity at that region to produce an efficient T-cell response.
Escaping the Immune System
Immunity to the Immune
- DFTD cells downregulate the expression of their MHC genes during establishment.
- Transcripts for immunosuppressive cytokines are expressed in the tumor cells that suppresses T-cell proliferation.
- If the MHC genes are down regulated then the tumor cells will not be recognized and suppressed T-cells also limit the immune responses.
Impacts
- Tasmanian Devils are Keystone species.
- As the tasmanian devil populations decline, the niches are available to other larger predators, competetors, and scavengers.
- The ecosystem will be changed drastically.
Management
- Healthy Captive population
- Translocation of healthy individuals
- Vaccine research
- Earlier breeding occurring in nature.
Management
Thank you
Reference:
Pye, R. J.; Woods, G. M.; Kreiss, A. Devil Facial Tumor Disease. Veterinary Pathology 2015, 53 (4), 726–736 DOI:10.1177/0300985815616444.