Canine Gliomas with Varying Immune Cell Levels Signal a Potential Immunotherapy Target

New research from North Carolina State University showed that high-grade gliomas contained more immune cells associated with suppressing immune response than low-grade gliomas. This evidence adds to previous research suggesting that these brain tumors may recruit cells that aid in immunosuppression. This research, published in Veterinary Pathology, is significant because it could inform future immunotherapy-based glioma treatments for humans and dogs.

More about Gliomas

Everyone has glial cells which are located throughout the brain and spinal cord. A glioma is formed when those cells become cancerous. In dogs, glioma is the second most common type of tumor in the central nervous system.

There are three different types of canine glioma, including oligodendroglioma, astrocytoma or undefined glioma. These can each be classified as high-grade or low-grade depending on certain microscopic features.

Using Immunotherapy to Treat Cancer

Immunotherapy is a powerful tool, using the body’s own immune system to attack the cancer. While immunotherapy has shown promise for treating some types of cancer, it has been relatively unsuccessful in treating glioma. This is likely because gliomas work by suppressing the immune system to facilitate tumor growth.

According to the first author and veterinary pathologist, Gregory Krane, “If we want to pursue immunotherapy for glioma, we first need to understand how these tumors interact with the immune system.” Current research is looking at this relationship to hopefully improve therapeutic outcomes.

The Research Study

The research team utilized immunohistochemical tagging and computerized image analysis to identify the numbers and type of immune cell in each of 73 different gliomas examined in the study. Types of immune cells include B lymphocytes, T lymphocytes, regulatory T lymphocytes (Tregs) and macrophages. The results showed a higher number of Tregs and polarized macrophages in high-grade tumors vs. low-grade tumors. There was no difference found in the other immune cells between different tumor types or grades.

“Tregs inhibit aspects of the immune response,” Krane says. “We hypothesize that Tregs may be involved in glioma-mediated immunosuppression, although that will require further research.”

The data also showed that the macrophage population in high-grade gliomas tended to be polarized toward the M2 phenotype. In general, M1-polarized macrophages are pro-inflammatory and anti-tumor, and M2-polarized macrophages are the opposite.

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

Understanding the Findings

This study may lead to a better understanding of how gliomas affect the immune system, which can eventually lead to improved immunotherapies for glioma in dogs and humas. The data provide support for utilizing canine patients with glioma to evaluate therapies that target Tregs or macrophage polarization as a potential treatment. Further research is needed, but this research makes strides towards understanding the relationship between gliomas and the immune system.

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