Research Study Update: Defining the Anti-Tumor Activity of Monocytes in Osteosarcoma
AKC Canine Health Foundation Grant 1903-A
Principal Investigator: Dr. Duncan Lascelles, PhD; North Carolina State University
Study suggest clear differences between the cell surface receptor expression of healthy dogs versus dogs with osteosarcoma
Osteosarcoma, the most common primary bone cancer in dogs, commonly affects large and giant breeds such as the Scottish Deerhound, Irish Wolfhound, Great Dane, Saint Bernard, Greyhound, Rottweiler, Boxer, Golden Retriever, and Labrador Retriever. With more than 8000 cases diagnosed per year in the United States, it is crucial that we constantly strive to improve the outcome of dogs affected by the disease. Unfortunately, survival times have not greatly improved over the last 20 years. Even after surgical tumor removal and chemotherapy, the cancer usually metastasizes and dogs often die of metastatic disease within an average of 12 months after diagnosis, despite aggressive therapy. Dr. Lascelles and colleagues made the interesting observation that survival times can double in osteosarcoma patients who develop infections associated with limb-spare surgeries. These infections may be capable of activating the immune system via monocytes (a type of white blood cell), to promote anti-tumor activity, as has been shown in mouse models. Therefore, we need to understand the role of monocytes in canine osteosarcoma in order to harness their anti-tumor capabilities.
To investigate this hypothesis further, these researchers characterized phenotypic (surface receptor expression) and functional differences of monocytes between normal dogs, and osteosarcoma dogs either with or without a concurrent infection. Preliminary data suggest clear differences between the cell surface receptor expression of normal versus untreated osteosarcoma dogs – osteosarcoma dogs have decreased expression of chemokine receptors on the surface of monocytes. These differences suggest that osteosarcoma may be capable of suppressing a monocyte’s capability to migrate out of the circulating blood, which in turn inhibits their ability to travel to the tumor where they could potentially exert anti-tumor activity. Similarly, they found that monocytes from untreated osteosarcoma dogs secrete higher levels of prostaglandin, which could suggest immunosuppression by the tumor, since prostaglandin has been reported to inhibit T-cell (another type of white blood cell) responses. Researchers plan to use these preliminary data to pursue funding of additional research funding in the near future.
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