Anyone who has seen the abscopal effect has got to be thinking that if we could turn this response on at will, the field of clinical oncology would be changed forever.
—James S. Welsh, MD
A deadly contagious cancer known as devil facial tumor disease is pushing the world’s largest carnivorous marsupial, the Tasmanian devil (Sarcophilius harrisii), to the brink of extinction. The loss of an interesting creature aside, the plight of the Tasmanian devil raises provocative questions about the oncogenic process and the transmission of cancer.
James S. Welsh, MD, a radiation oncologist with the Northern Illinois University Neutron Therapy Facility at Fermilab, spoke with The ASCO Post about how immune responses to “contagious cancer” might someday play a principal role in oncology.
What sparked your interest in contagious cancer?
My interest in cancers spread among animals began quite some time ago, mainly as a zoology and ecology curiosity, but it was evident that animal cancers could serve as a model for human cancers. And the pioneering work on oncogenic retroviruses that led to the discovery of oncogenes set the stage for our modern understanding of the molecular mechanisms of cancer.
Recently, the discovery of contagious cancers, including the devil facial tumor disease, which might lead to extinction of the Tasmanian devil in the wild, has rekindled my curiosity. Eventually, I became convinced that underlying mechanisms in the transmission of animal-to-animal cancers might have value in clinical oncology, particularly in the area of immunotherapy.
Origin of Devil Facial Tumor Disease
What kind of cancer is being transmitted among Tasmanian devils?
Devil facial tumors are head and neck cancers. The cells are probably of neural crest origin, perhaps from Schwann cells. Similar to human head and neck cancers, they are locally destructive and they spread to regional lymph nodes, occasionally metastasizing to the lungs if the animal lives that long.
We don’t know the origin of this tumor, but the first pathologically confirmed case of devil facial tumor disease was in 1997. We do know that these cancers are typically transmitted as an allograft when the face is bitten during territorial fights and courtship battles. Malignant cells are found on the gums and teeth of affected animals and can be directly transplanted into the wound of another animal by a bite.
A lot of people assume that devil facial tumor disease is a head and neck cancer that originally arose in that region, but I have my own hypothesis. This tumor might have arisen in a different organ in the index animal. We know that Tasmanian devils are prone to cannibalism, so it could be that one animal ate the index animal and tumor tissue got lodged in its teeth and gums. That tumor tissue developed into the cancer and was then transmitted to other animals during fighting. And that’s how I believe the disease became entrenched in the head and neck region of these animals.
The locally aggressive malignancy often causes death within 6 months due to consequences of airway obstruction and inability to feed. It’s important to note that in little more than 10 years the cancer has spread so rapidly that the Tasmanian devil has been placed on the endangered species list, which is quite remarkable.
Other Contagious Cancers
Are there other contagious cancers notable among animals?
Several. One is among dogs, called canine transmissible venereal tumor, also known as Sticker’s sarcoma. There are similarities between this cancer and devil facial tumor disease in that it is passed from animal to animal and is not caused by a virus or another infectious agent. But unlike devil facial tumor disease, which is rapidly progressive and fatal, the canine cancer progresses rapidly at first, then regresses, and is not usually fatal.
We don’t know exactly why this cancer acts this way, but it is postulated that there might be an initial downmodulation of major histocompatibility complex (MHC) antigens, which reduces its initial visibility to the host’s immune system. Interestingly, the MHC class 2 antigens are later reexpressed, and the dog’s immune system is alerted and rejects the tumor, which is a very different outcome from the cancer that has so far wiped out half of the wild population of the Tasmanian devil.
Impact of Immunology
Immunology receives mixed reviews in oncology. Do you believe there’s some potential there that we’re not yet seeing?
I do, and a recent New England Journal of Medicine paper on the abscopal effect (ie, when local therapy directed at a tumor site is associated with regression of metastases elsewhere in the body) in a patient with melanoma further accelerated my interest and scientific belief in the underlying power of immune responses.1 I, and many radiation oncologists, have observed the abscopal phenomenon. For example, I was irradiating a bone metastasis in an end-stage patient to palliate his symptoms, and almost miraculously most of his metastatic disease disappeared. It left me scratching my head, wondering what had just happened.
What did happen?
We know that the immune system somehow woke up, recognized the cancer as something that doesn’t belong in the body, and eradicated it in much the same way it would attack a transplanted organ. Unfortunately these abscopal responses happen infrequently, and when they do occur, they typically don’t last long, although sometimes the response is durable. Anyone who has seen the abscopal effect has got to be thinking that if we could turn this response on at will, the field of clinical oncology would be changed forever.
Pursuing the Mystery
If we take the immune responses demonstrated in the abscopal effect and the canine cancer, is there a scientific clue that might lead to more extensive work in immunology?
I’m not an immunologist, but I’ve come to believe that if we pursue this intriguing biologic mystery, we’ll discover a critical sign that will allow us to switch on the abscopal effect that I and other radiation oncologists have seen firsthand. As mentioned, it leaves you in wonderment.
Moreover, the fact that Sticker’s sarcoma in canines disappears spontaneously after the immune system is alerted—as opposed to the Tasmanian devil cancer, which acts more like the cancers we see in humans—seems to indicate that in the space between the polar opposite outcomes there might be a clue that will allow us to exploit our immune system’s ability to eradicate cancers.
Role of Vaccines
We know that about 15% of cancers worldwide are caused by infectious etiologies. Do you see a greater role for vaccines moving forward?
Absolutely. The rise in head and neck cancers among a younger population that don’t have the classic carcinogenic risk factors is due to human papillomavirus infection. If that’s the case, there’s going to be a very important role for vaccination. And as we gain more knowledge in this area, I’m sure that vaccines will prove effective in a growing number of virally transmitted cancers.
Any last thoughts on contagious cancer and the immune system?
The story of animal-to-animal transmission of malignancies is fascinating in that we see two starkly different outcomes—one that is rapidly fatal and one that is mediated by an immune response that makes the cancer completely regress. Then there’s the abscopal effect in humans, which further demonstrates the immune system’s uncanny ability to kill cancers.
Also, as a clinician, I’ve been fascinated by the occasional mother-to-fetus transmission of cancers such as lymphoma and leukemia. Even more rare is the transmission of cancers from donor to patient in organ transplants. Interestingly, if the donated organ is from a person with cancer, and the organ recipient subsequently develops cancer from that organ, sometimes when the immunosuppression is stopped and the donated organ is removed, the cancer will regress—even after metastasis.
So that response is akin to dogs with Sticker’s sarcoma, in which the immune system wakes up and rejects the malignancy. In other words, if the immune system is not immunosuppressed to prevent it from rejecting the transplanted organ, it may also reject the transplanted cancer.
Combining these various observations about transmission and immune response might someday provide valuable clues that can be translated into breakthroughs in the clinic. ■
Disclosure: Dr. Welsh is on the Advisory Committee for the Medical Use of Isotopes, United States Nuclear Regulatory Commission.
1. Postow MA, Callahan MK, Barker CA, et al: Immunologic correlates of the abscopal effect in a patient with melanoma. N Engl J Med 366:925-931, 2012.
The term “abscopal” is from Greek roots that mean “away from the target.” Coined by R.H. Mole in 1953, it was used to label observed effects of radiation at a distance from the volume irradiated. Mounting evidence suggests an immunologic basis for the effect, but it should also be remembered that...