Brain cancer: Why glioblastoma doesn't respond well to immunotherapy

Evan Walker
Evan Walker TheMediTary.Com |
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Researchers continue to search for better ways to treat brain cancers such as glioblastoma. Bloomberg Creative/Getty Images
  • New research shows why immunotherapy can be effective at treating cancerous tumors that spread to the brain while glioblastoma – a cancer that originates in the brain – doesn’t respond well to such treatments.
  • Tumors that originate elsewhere in the body are “primed” to respond to immunotherapy while glioblastoma doesn’t have this characteristic.
  • Future research, early intervention, and personalized therapies can help increase understanding, along with improving survival rates.

New research out of the University of California Los Angeles (UCLA) could help aid our understanding of why some cancerous brain tumors respond well to immunotherapy while others do not.

Researchers from UCLA’s Jonsson Comprehensive Cancer Center shared their data today in the Journal of Clinical Investigation.

They investigated why glioblastoma – an aggressive cancer that originates in the brain – is so difficult to treat while other brain tumors respond well to immunotherapy treatment.

“The reasoning to do this work was mainly to see what the anti-tumor immune response was like in cancers where immunotherapy is known to elicit true clinical responses, then we could compare and contrast with the anti-tumor immune response in primary brain tumors like glioblastoma in which immunotherapy does not typically induce a clinically meaningful impact,” said Robert Prins, PhD, a senior study author and a professor of molecular and medical pharmacology and neurosurgery at the David Geffen School of Medicine at UCLA.

Researchers said they hope the data can pave the way to an improved understanding of the mechanisms at play between immunotherapy and brain tumors.

A significant difference between glioblastoma and other cancerous tumors that affect the brain is that glioblastoma originates in the brain, whereas other tumors often originate elsewhere in the body and spread to the brain.

Immunotherapy is often effective when treating other tumors, but it generally fails to elicit a response in people with glioblastoma.

Prins told Medical News Today that in tumors that originated outside the brain before spreading, T cells – white blood cells critical to immune response – had been activated by lymph nodes, a “priming” process that helps immunotherapy attack the tumor.

A possible avenue to improved treatments for glioblastoma, said Prins, could be to try to recreate this process in a lab environment.

“[The process involves] generating dendritic cells from patients in the lab, pulsing them with tumor-specific proteins, and then re-injecting them back into the same patient,” he explained.

Naveed Wagle, a neuro-oncologist at Providence Saint John’s Health Center and an associate professor of Translational Neurosciences at Saint John’s Cancer Institute in California who was not involved in the study, told Medical News Today that the data sheds light on the differences between immune cells in the brain versus immune systems elsewhere in the body.

“Immunotherapy is still somewhat efficacious [when treating tumors that have spread to the brain] because it’s the same pathway that the original cells were using to grow, and the body and immune cells were primed for it,” he said. “Glioblastoma originates in the brain, which makes it resistant to a lot of the therapies that might work if it was elsewhere in the body. This study is showing that the origination of immune cells that were intrinsic to the brain may in fact be a different process by which the brain deals with injuries in the rest of the body.”

Part of the challenge in treating glioblastoma comes in the blood-brain barrier, which effectively means that immune system cells and brain cells don’t speak the same language.

“The blood-brain barrier is a protective layer that prevents many substances from entering the brain, including some drugs that could potentially treat brain tumors,” explained Dr. Wael Harb, a hematologist and medical oncologist at MemorialCare Cancer Institute at Orange Coast Medical Center in California who was not involved in the study. “Therefore, delivering effective doses of drugs to the tumor site can be challenging and may require novel strategies.”

Harb told Medical News Today that the genetic diversity of brain tumors can make them resistant to therapies, underlining the need for personalized treatments that match each patient’s tumor profile, along with continuous monitoring.

Early intervention can also be a challenge.

“The lack of effective biomarkers for early detection and monitoring of brain tumors [is a challenge],” said Harb. “Therefore, finding reliable and non-invasive ways to diagnose brain tumors at an early stage and tracking their response to therapy can be beneficial for improving survival rates.”

Glioblastoma is one of many forms of cancer that progress quickly, resist interventions, and ultimately result in death. But even though there’s no cure or magic bullet on the immediate horizon, experts say the UCLA data has added to the body of knowledge surrounding it.

“I think we’re making progress,” said Wagle. “Glioblastoma has been something that’s been very difficult and we’re still making a lot of progress in understanding it. I think in the near future, we’ll see a lot of new therapies that hopefully will be much more efficacious, and I think they’re just around the corner.”

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