778: Role of Regulatory T Cells in Dogs with Osteosarcoma

Grant Status: Closed

Grant Amount: $67,388.48
Dr. Barbara J Biller, D.V.M., Colorado State University
April 1, 2007 - September 30, 2009
Sponsor(s): American Belgian Tervuren Club, Inc., American Bloodhound Club, American Pointer Club, American Shetland Sheepdog Association, American Spaniel Club Foundation, Australian Shepherd Health & Genetics Institute, English Cocker Spaniel Club of America, English Springer Spaniel Field Trial Association Foundation, Estate of Dr. Judith Musladin, Estate of Virginia Lyn Tarquinio, German Wirehaired Pointer Club of America, Greyhound Club of America, Miniature Pinscher Club of America, Inc., National Beagle Club, Poodle Club of America Foundation, Portuguese Water Dog Club of America, Inc., Siberian Husky Club of America, Toby's Foundation, United States Australian Shepherd Association, United States Australian Shepherd Foundation, Vizsla Club of America Welfare Foundation, Welsh Springer Spaniel Club of America
Breed(s): -All Dogs
Research Program Area: Treatment

Project Summary

The primary goal of this study was to investigate a specific type of lymphocyte, known as a regulatory T cell (Treg), in dogs with osteosarcoma (OSA). Treg are known to be present in abnormally high numbers in human cancer patients where they have been shown to interfere with the immune system�s ability to detect and kill cancerous cells. In addition, determination of Treg levels can provide prognostic (predictive) information for many types of human malignancies. Our objectives for this project were to: 1) determine whether dogs with OSA have high numbers of Treg compared to healthy dogs, 2) determine if surgical removal of the tumor (limb amputation) or the type of chemotherapy given after surgery changed Treg numbers compared to their pre-treatment values, and 3) evaluate whether OSA dogs with high Treg numbers had a poorer prognosis than dogs with low numbers of Treg. We enrolled a total of 18 dogs with OSA and followed their progress through the study and afterwards. We also compared Treg and other important T lymphocyte subsets (CD4+ and CD8+ T cells) between the dogs with cancer and 22 healthy control dogs. We found that dogs with OSA had significantly more Treg in their blood compared to healthy dogs. Although removal of the tumor did not change Treg numbers within a 24 hour period following surgery, there was a significant increase in Treg between pre-treatment blood samples and those collected 7 - 10 days after the first chemotherapy treatment. This suggests that Treg numbers may continue to rise despite the initiation of treatment for OSA. One of the most important findings to emerge from this study was that determination of the ratio of the percent of CD8+ T cells (a subset of T lymphocytes) to the percent of Treg was predictive for survival (short versus long) in the dogs with OSA. This ratio has been used to determine outcome in some types of human cancers but this is the first time we have applied this ratio to better understand cancer in dogs. This information could be very useful to veterinary professionals in helping owners of dogs with OSA make informed treatment decisions.

Publication(s)

Biller, B., Guth, A., Burton, J., Dow, S., 2010, Decreased Ratio of CD8+ T Cells to Regulatory T Cells Associated with Decreased Survival in Dogs with Osteosarcoma. Journal of Veterinary Internal Medicine 24, 1118-1123.

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