Study finds therapeutic targets in canine brain tumors

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Washington [US], Aug. 22 (ANI): High-grade gliomas, or brain tumors, in dogs contain more immune cells associated with suppressing the immune response than low-grade gliomas, new study finds.

The work, which was published in the journal Veterinary Pathology, is the most in-depth examination of immune cell infiltration in canine glioma to date, adding to the body of evidence that these brain tumors could recruit cells that help immunosuppression. The findings could have implications for future immunotherapy-based glioma treatments in humans and dogs.

Glial cells are support cells located throughout the brain and spinal cord. When these cells become cancerous, the resulting tumor is called a glioma. In dogs, gliomas are the second most common type of tumor in the central nervous system and account for about 35% of all intracranial cancers.

The median survival time for dogs with glioma treated with radiation therapy ranges from nine to 14 months, which is similar to the median survival time of 14 months for humans treated with a combination of surgery, radiation therapy, and chemotherapy.

There are three types of canine glioma: oligodendroglioma, astrocytoma, or indefinite glioma. Each of these subtypes can be further classified into low or high quality based on certain microscopic characteristics. Although the subtype and grade of glioma affect survival and choice of treatment in humans, it is currently not known whether the same is true for dogs.

Immunotherapy harnesses the power of the body’s immune system to attack cancer. Although immunotherapy has shown promise in some types of cancer, it has not been successful in glioma in humans, possibly because gliomas have been shown to suppress the immune system in order to to facilitate tumor growth.

Researchers are trying to better understand the interaction between glioma and the immune system in hopes of improving treatment outcomes.

“If we are to pursue immunotherapy for glioma, we must first understand how these tumors interact with the immune system,” said Gregory Krane, senior research author and veterinary pathologist who recently received his PhD from North Carolina State University.

Krane added, “There are many common features between canine and human glioma, which makes research on the immune system in canine glioma a good approach to answer questions about this cancer in humans and dogs. The multi-institutional research team examined 73 different gliomas. obtained from veterinary patients seen at NC State College of Veterinary Medicine between 2006 and 2018. Using immunohistochemical staining and computerized image analysis, the team identified the number of each cell type immune in each tumor: B lymphocytes, T lymphocytes, regulatory T lymphocytes (Tregs) and macrophages.

The team found higher numbers of Tregs and polarized macrophages in high-grade and low-grade tumors, but no difference in other immune cells between different tumor types or grades.

“Tregs inhibit some aspect of the immune response,” Krane said. “In healthy individuals, it prevents autoimmune disease. But cancers can recruit and activate Tregs to prevent the immune system from attacking the tumor. We found that Tregs were more abundant in high gliomas. grade than in low-grade gliomas. We hypothesize that Tregs may be involved in glioma-induced immunosuppression, although this will require additional research. “The research team also counted the number of macrophages in each tumor, which can be polarized at either end of a spectrum called M1 or M2 polarization. In a general sense, M1 polarized macrophages are pro-inflammatory and anti-tumor, and M2 polarized macrophages are at the opposite.

They found that the macrophage population in high grade gliomas tended to be polarized towards the M2 phenotype.

“These macrophage polarization data may expand the glioma immunosuppression hypothesis by providing another mechanism by which gliomas can suppress the dog’s immune system,” says Krane.

Krane hopes this study may lead to a better understanding of how gliomas affect the immune system and possibly improved immunotherapies for gliomas.

“Using the dog as a preclinical model to understand the immune response to glioma could lead to treatments that will help both dogs and humans,” Krane said. “Although more work is needed, our data provide some support for using canine glioma patients to evaluate therapies targeting Tregs or macrophage polarization designed for use in humans.” The study was supported by the National Toxicology Program of the National Institute of Environmental Health Sciences (NIEHS / NTP), NC State’s College of Veterinary Medicine, and Charles River Laboratories. Christopher Mariani, associate professor of neurology at NC State and principal investigator of the comparative laboratory of neuroimmunology and neuro-oncology at NC State, is the corresponding author.

The other North Carolina State co-authors were Associate Professors of Pathology David Malarkey and Debra Tokarz and veterinarian student Britani Raines. Researchers from NIEHS / NTP, Charles River Laboratories, University of Alabama at Birmingham, Cornell University and Integrated Laboratory Systems co-authored the work. (ANI)


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