Varying immune cell levels in canine brain tumors could provide
therapeutic targets

Date:
August 19, 2021
Source:
North Carolina State University
Summary:
A new study reveals that high-grade gliomas, or brain tumors,
in dogs contained more immune cells associated with suppressing
immune response than low-grade gliomas.



FULL STORY ==========================================================================
A new study reveals that high-grade gliomas, or brain tumors, in dogs
contained more immune cells associated with suppressing immune response
than low-grade gliomas. The work, which is the most extensive examination
of immune cell infiltration in canine glioma to date, adds to the body
of evidence that these brain tumors might recruit cells that aid in immunosuppression. The findings could have implications for future immunotherapy-based glioma treatments 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. In dogs, gliomas are the second most common type of tumor in
the central nervous system and represent about 35% of all intracranial
cancers. Median survival time for dogs with glioma treated with radiation therapy ranges from nine to 14 months, which is similar to the 14 month
median survival time for humans treated with a combination of surgery, radiation and chemotherapy.

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

Immunotherapy harnesses the power of the body's immune system to attack
cancer.

Though immunotherapy has shown promise in certain types of cancers, it
hasn't been successful in glioma in humans, possibly because gliomas
have been shown to suppress the immune system in order to facilitate
tumor growth. Researchers are trying to better understand the interaction between glioma and the immune system with hopes of improving therapeutic outcomes.

"If we want to pursue immunotherapy for glioma, we first need to
understand how these tumors interact with the immune system," says
Gregory Krane, first author of the research and a veterinary pathologist
who recently received his Ph.D.

from North Carolina State University. "There are many shared features
between canine and human glioma, which makes researching the immune
system in canine glioma a good approach to addressing questions about
this cancer in both humans and dogs." The multi-institutional research
team examined 73 different gliomas obtained from veterinary patients
seen at the NC State College of Veterinary Medicine between 2006 and
2018. Utilizing immunohistochemical tagging and computerized image
analysis, the team identified the numbers of each type of immune cell 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- versus low-grade tumors, but no differences for
other immune cells between different tumor types or grades.

"Tregs inhibit aspects of the immune response," Krane says. "In healthy individuals, this 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-grade gliomas than
in low-grade gliomas.

We hypothesize that Tregs may be involved in glioma-mediated
immunosuppression, although that will require further research."
The research team also counted the number of macrophages in each tumor,
which can be polarized to either end of a spectrum referred to as M1
or M2 polarization. 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 be polarized towards the M2 phenotype.

"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.

Krane is hopeful that this study may lead to a better understanding
of how gliomas affect the immune system, and eventually to improved immunotherapies for glioma. "Using the dog as a preclinical model for understanding the immune response to glioma could lead to treatments
that will help both dogs and people," Krane says. "Though further work
is needed, our data provide some support to utilize canine patients with
glioma to evaluate therapies targeting Tregs or macrophage polarization designed for use in humans." The research was published online in
July 2021 in Veterinary Pathology and was supported by the National
Institute of Environmental Health Sciences' National Toxicology Program (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 NC State's Comparative Neuroimmunology
and Neuro-oncology Laboratory, is corresponding author. Other NC State co-authors were associate professors of pathology David Malarkey and Debra Tokarz, and veterinary student Britani Rainess. Researchers from NIEHS/
NTP, Charles River Laboratories, the University of Alabama at Birmingham, Cornell University and Integrated Laboratory Systems coauthored the work.

========================================================================== Story Source: Materials provided by
North_Carolina_State_University. Original written by Tracey Peake. Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Gregory A. Krane, Carly A. O'Dea, David E. Malarkey, Andrew
D. Miller, C.

Ryan Miller, Debra A. Tokarz, Heather L. Jensen, Kyathanahalli S.

Janardhan, Keith R. Shockley, Norris Flagler, Brittani A. Rainess,
Christopher L. Mariani. Immunohistochemical evaluation of immune
cell infiltration in canine gliomas. Veterinary Pathology, 2021;
030098582110239 DOI: 10.1177/03009858211023946 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/08/210819125256.htm

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