A Histological and Immunohistochemical Analysis of Lymphoid Tissues of the Tasmanian Devil

Kreiss, Alexandre; Obendorf, David; Hemsley, Susan; Canfield, P. J.; Woods, Gregory M.

doi:10.1002/ar.20896

Cited by 25 publications

(31 citation statements)

References 31 publications

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“…Lymphoid organs, including the thymus, spleen, and lymph nodes, were identified in all animals, including juveniles, and all structures were similar in appearance to those in placental mammals (32,33). T lymphocytes expressed cell surface CD3, monocytes expressed MHC class II (MHC-II), and B lymphocytes expressed CD79 (34). Identification of lymphocyte subsets required the development of specific mAbs (35).…”

Section: Dftd Transmission and Immunology Of Tasmanian Devilsmentioning

confidence: 90%

Immunology of a Transmissible Cancer Spreading among Tasmanian Devils

Woods

Howson

Brown

et al. 2015

The Journal of Immunology

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Devil facial tumor disease (DFTD) is a transmissible cancer that has killed most of the Tasmanian devil (Sarcophilus harrissii) population. Since the first case appeared in the mid-1990s, it has spread relentlessly across the Tasmanian devil’s geographic range. As Tasmanian devils only exist in Tasmania, Australia, DFTD has the potential to cause extinction of this species. The origin of DFTD was a Schwann cell from a female devil. The disease is transmitted when devils bite each other around the facial areas, a behavior synonymous with this species. Every devil that is ‘infected’ with DFTD dies from the cancer. Once the DFTD cells have been transmitted, they appear to develop into a cancer without inducing an immune response. The DFTD cancer cells avoid allogeneic recognition because they do not express MHC class I molecules on the cell surface. A reduced genetic diversity and the production of immunosuppressive cytokines may also contribute.

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Section: Dftd Transmission and Immunology Of Tasmanian Devilsmentioning

confidence: 90%

Immunology of a Transmissible Cancer Spreading among Tasmanian Devils

Woods

Howson

Brown

et al. 2015

The Journal of Immunology

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“…In tumours with changed MHC profile, NK cells are activated and promote the killing of abnormal cells [54]. Although devils possess the expected range of immune cells [55], NK cell function has still to be explored in the Tasmanian devil. Tumours can utilise other mechanisms to evade immune recognition.…”

Section: Discussionmentioning

confidence: 99%

Allorecognition in the Tasmanian Devil (Sarcophilus harrisii), an Endangered Marsupial Species with Limited Genetic Diversity

et al. 2011

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Tasmanian devils (Sarcophilus harrisii) are on the verge of extinction due to a transmissible cancer, devil facial tumour disease (DFTD). This tumour is an allograft that is transmitted between individuals without immune recognition of the tumour cells. The mechanism to explain this lack of immune recognition and acceptance is not well understood. It has been hypothesized that lack of genetic diversity at the Major Histocompatibility Complex (MHC) allowed the tumour cells to grow in genetically similar hosts without evoking an immune response to alloantigens. We conducted mixed lymphocyte reactions and skin grafts to measure functional MHC diversity in the Tasmanian devil population. The limited MHC diversity was sufficient to produce measurable mixed lymphocyte reactions. There was a wide range of responses, from low or no reaction to relatively strong responses. The highest responses occurred when lymphocytes from devils from the east of Tasmania were mixed with lymphocytes from devils from the west of Tasmania. All of the five successful skin allografts were rejected within 14 days after surgery, even though little or no MHC I and II mismatches were found. Extensive T-cell infiltration characterised the immune rejection. We conclude that Tasmanian devils are capable of allogeneic rejection. Consequently, a lack of functional allorecognition mechanisms in the devil population does not explain the transmission of a contagious cancer.

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“…The PBMC layer was then collected and washed 2× with RPMI at 500 g for 5 min. Formalin-fixed paraffin-embedded (FFPE) tissue sections were collected and processed as reported previously (3, 27). …”

Section: Methodsmentioning

confidence: 99%

PD-L1 Is Not Constitutively Expressed on Tasmanian Devil Facial Tumor Cells but Is Strongly Upregulated in Response to IFN-γ and Can Be Expressed in the Tumor Microenvironment

et al. 2016

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The devil facial tumor disease (DFTD) is caused by clonal transmissible cancers that have led to a catastrophic decline in the wild Tasmanian devil (Sarcophilus harrisii) population. The first transmissible tumor, now termed devil facial tumor 1 (DFT1), was first discovered in 1996 and has been continually transmitted to new hosts for at least 20 years. In 2015, a second transmissible cancer [devil facial tumor 2 (DFT2)] was discovered in wild devils, and the DFT2 is genetically distinct and independent from the DFT1. Despite the estimated 136,559 base pair substitutions and 14,647 insertions/deletions in the DFT1 genome as compared to two normal devil reference genomes, the allograft tumors are not rejected by the host immune system. Additionally, genome sequencing of two sub-strains of DFT1 detected greater than 15,000 single-base substitutions that were found in only one of the DFT1 sub-strains, demonstrating the transmissible tumors are evolving and that generation of neoantigens is likely ongoing. Recent evidence in human clinical trials suggests that blocking PD-1:PD-L1 interactions promotes antitumor immune responses and is most effective in cancers with a high number of mutations. We hypothesized that DFTD cells could exploit the PD-1:PD-L1 inhibitory pathway to evade antitumor immune responses. We developed recombinant proteins and monoclonal antibodies (mAbs) to provide the first demonstration that PD-1 binds to both PD-L1 and PD-L2 in a non-placental mammal and show that PD-L1 is upregulated in DFTD cells in response to IFN-γ. Immunohistochemistry showed that PD-L1 is rarely expressed in primary tumor masses, but low numbers of PD-L1+ non-tumor cells were detected in the microenvironment of several metastatic tumors. Importantly, in vitro testing suggests that PD-1 binding to PD-L1 and PD-L2 can be blocked by mAbs, which could be critical to understanding how the DFT allografts evade the immune system.

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A Histological and Immunohistochemical Analysis of Lymphoid Tissues of the Tasmanian Devil

Cited by 25 publications

References 31 publications

Immunology of a Transmissible Cancer Spreading among Tasmanian Devils

Immunology of a Transmissible Cancer Spreading among Tasmanian Devils

Allorecognition in the Tasmanian Devil (Sarcophilus harrisii), an Endangered Marsupial Species with Limited Genetic Diversity

PD-L1 Is Not Constitutively Expressed on Tasmanian Devil Facial Tumor Cells but Is Strongly Upregulated in Response to IFN-γ and Can Be Expressed in the Tumor Microenvironment

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