University of Calgary scientists at the Arnie Charbonneau Cancer Institute at the Cumming School of Medicine (CSM) have discovered a way to stop the growth of glioblastoma, the deadliest form of brain cancer. The finding, published in Nature Communications, provides a new tactic in the war against cancer that involves reprogramming the immune system to do what it does best fight the tumour instead of fuelling it.
For some time, scientists have observed a tumour's ability to recruit cells from the immune system. Until now, they did not understand how the tumour was able to do that.
"We discovered that glioblastoma cells secrete a specific factor, called interleukin 33," says Dr. Stephen Robbins, PhD, co-principal investigator on the study, and professor at the CSM. "It's this substance that draws immune cells to the tumour and helps to create an environment that changes the function of the immune cells. Instead of fighting the tumour, the immune cells go to work for it, contributing to the tumour's rapid growth."
Co-leads Stephen Robbins and Donna Senger, with co-first authors Bo-Young Ahn and Astrid De Boeck. Photo by Kelly Johnston, Cumming School of Medicine
Interleukin 33 (IL-33) is not new to researchers. It is referred to as an alarmin. Just like it sounds, alarmin raises an alarm in the body that signals the immune system. The research, conducted in mice, shows that when the tumour cells release IL-33 it signals the immune cells to the tumour.
However, its job does not stop there, IL-33 also works in the nucleus of the tumour cell, which is critical, as it is this change that triggers the transformation in the immune cells, altering their function from fighting tumour growth to promoting it.
Bo-Young Ahn defined a role for IL-33 in glioma progression. Photo by Kelly Johnston, Cumming School of Medicine
Current treatment for glioblastoma includes surgery, radiation, and chemotherapy, which can be effective, but is not curative. This type of tumour is very resilient; however, the researchers found that there is a way to stop the tumour's growth.
"We found that by stopping IL-33 from reaching the nucleus of the tumour cell, it crippled the entire process," says Dr. Donna Senger, PhD, co-principal investigator on the study, and research associate professor at the CSM. "When we interrupt this step, the immune cells come into the tumour and can do the job they were meant to do: Attack the cancer."
When the IL-33 process was disrupted, survival rates increased to over a year, from two months or less. While this study was in mice, glioblastomas in people behave similarly. The researchers say this discovery provides an additional strategy for the medical community to consider to contain and possibly destroy this fatal cancer.
Astrid De Boeck identified IL-33 as an inflammatory mediator in brain tumours. Photo by Kelly Johnston, Cumming School of Medicine
"New findings like this one advances our fundamental understanding of how we can potentially re-program our immune system precisely to attack and destroy glioblastoma and other cancers," says Dr. Victor Ling, Terry Fox Research Institute (TFRI) president and scientific director.
"Our congratulations to this pan-Canadian team, led from the University of Calgary, for demonstrating how translational cancer research built on collaboration, and open and transparent data sharing, can have profound results."
Robbins and Senger add that this finding can help shift the conversation and approach to fighting cancer to move beyond targeting the cancer cell to now include the host immune system as part of the artillery.
TFRI funded this pan-Canadian glioblastoma team from 2012 to 2019. This study is also supported by the Alberta Cancer Foundation, Alberta Innovates, Genome B.C. and the Canadian Institutes of Health Research (CIHR).
Stephen Robbins is a professor in the departments of Oncology, and Biochemistry and Molecular Biology and a member of the Arnie Charbonneau Cancer Institute at the CSM. He is the scientific director of the CIHR Institute of Cancer Research.
Donna Senger is a research associate professor in the Department of Oncology and a member of Arnie Charbonneau Cancer Institute at the CSM.
