A new study reveals that high-grade gliomas, or brain tumors, in dogscontained more immune cells associated with suppressing immune response thanlow-grade gliomas. The work, which is the most extensive examination of immunecell infiltration in canine glioma to date, adds to the body of evidence thatthese brain tumors might recruit cells that aid in immunosuppression. Thefindings could have implications for future immunotherapy-based gliomatreatments in both humans and dogs.

Glial cells are support cells located throughout the brain and spinal cord.When those cells become cancerous, the resulting tumor is called a glioma. Indogs, gliomas are the second most common type of tumor in the central nervoussystem and represent about 35% of all intracranial cancers. Median survivaltime for dogs with glioma treated with radiation therapy ranges from nine to14 months, which is similar to the 14 month median survival time for humanstreated with a combination of surgery, radiation and chemotherapy.

There are three types of canine glioma: oligodendroglioma, astrocytoma orundefined glioma. Each of these subtypes can be further classified as low orhigh-grade based on certain microscopic features. Although glioma subtype andgrade affect survival and treatment choice in humans, it is currently unknownwhether the same is true for dogs.

Immunotherapy harnesses the power of the body’s immune system to attackcancer. Though immunotherapy has shown promise in certain types of cancers, ithasn’t been successful in glioma in humans, possibly because gliomas have beenshown to suppress the immune system in order to facilitate tumor growth.Researchers are trying to better understand the interaction between glioma andthe immune system with hopes of improving therapeutic outcomes.

“If we want to pursue immunotherapy for glioma, we first need to understandhow these tumors interact with the immune system,” says Gregory Krane, firstauthor of the research and a veterinary pathologist who recently received hisPh.D. from North Carolina State University. “There are many shared featuresbetween canine and human glioma, which makes researching the immune system incanine glioma a good approach to addressing questions about this cancer inboth humans and dogs.”

The multi-institutional research team examined 73 different gliomas obtainedfrom veterinary patients seen at the NC State College of Veterinary Medicinebetween 2006 and 2018. Utilizing immunohistochemical tagging and computerizedimage analysis, the team identified the numbers of each type of immune cell ineach tumor: B lymphocytes, T lymphocytes, regulatory T lymphocytes (Tregs) andmacrophages. The team found higher numbers of Tregs and polarized macrophagesin high- versus low-grade tumors, but no differences for other immune cellsbetween different tumor types or grades.

“Tregs inhibit aspects of the immune response,” Krane says. “In healthyindividuals, this prevents autoimmune disease. But cancers can recruit andactivate Tregs to prevent the immune system from attacking the tumor. We foundthat Tregs were more abundant in high-grade gliomas than in low-grade gliomas.We hypothesize that Tregs may be involved in glioma-mediatedimmunosuppression, although that will require further research.”

The research team also counted the number of macrophages in each tumor, whichcan be polarized to either end of a spectrum referred to as M1 or M2polarization. In a general sense, M1-polarized macrophages are pro-inflammatory and anti-tumor, and M2-polarized macrophages are the opposite.They found that the macrophage population in high-grade gliomas tended to bepolarized towards the M2 phenotype.

“These macrophage polarization data can expand the glioma immunosuppressionhypothesis by providing another mechanism by which gliomas may suppress theimmune system in the dog,” Krane says.

Krane is hopeful that this study may lead to a better understanding of howgliomas affect the immune system, and eventually to improved immunotherapiesfor glioma. “Using the dog as a preclinical model for understanding the immuneresponse to glioma could lead to treatments that will help both dogs andpeople,” Krane says. “Though further work is needed, our data provide somesupport to utilize canine patients with glioma to evaluate therapies targetingTregs or macrophage polarization designed for use in humans.”

The research was published online in July 2021 in Veterinary Pathology.

Image: Credit: CC0 Public Domain

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