SEP 05, 2023 8:00 AM PDT

New Research Explains Limitation of Immunotherapy Against Brain Tumors

Cancer is a deadly disease with multiple risk factors. Risk factors are dependent on the type of cancer and each one is treated differently. The heterogeneity of various cancers is the main reason there is no cure. Additionally, cancer evolves and can also come back after being treated and lying dormant for years. Therefore, it is very difficult to find an effective treatment that provides high quality of life for patients.

One aggressive cancer that is difficult to treat includes glioblastoma. This brain tumor is fast-growing and results in the form of many different symptoms including headache, vomiting, and seizures. Unfortunately, there is not much known on glioblastoma. The cause of this disease is unclear and treatment options are limited. This tumor stays in the brain and does not metastasize, but because of its location, glioblastoma is hard to treat. Currently, treatment options include radiation, chemotherapy, and surgery with limited success. Even immunotherapy, a more recent treatment, which activates the body’s immune system to kill the tumor has limited efficacy in the brain.

A group of researchers led by Dr. Robert Prins at the David Geffen School of Medicine at University of California Los Angeles (UCLA) recently published an article in the Journal of Clinical Investigation (JCI) describing new research that could help overcome obstacles to glioblastoma treatment. More specifically, Prins and colleagues have reported why glioblastoma that originates from other parts of the body respond better to immunotherapy compared to glioblastoma that originates in the brain.

The researchers took nine patients with metastatic brain tumors that were responsive to immunotherapy and compared them to nineteen patients with metastatic brain tumors that were not responsive to immunotherapy. Prins and colleagues used a technology called RNA-sequencing, which shows the genes upregulated in different cell populations. After running RNA-sequencing on the samples they gathered, they compared those samples with twenty-five patient samples with recurrent brain tumors. The goal was to determine which cells were changing with treatment compared to others. Interestingly, no one has before compared the effects of immunotherapy on brain tumor patient samples in this context.

The results showed that with immunotherapy tumors that originated in a different area of the brain had more T cells, an immune cell responsible for killing pathogens in the body. These T cells were associated with activation of tumor killing. They also found that these patients had prolonged survival compared to patients with brain tumors that originated in the brain, including glioblastoma. The immunotherapy did not work when physicians tried to treat glioblastoma. Researchers believe that they can use this knowledge to better target metastatic brain tumors. More specifically, since there are more T cells in brain tumors that originated from other areas of the body, immunotherapies can be utilized to more effectively target those cells to kill the tumor. Additionally, tumors that are known to metastasize can be aggressively treated before ever reaching the brain.

Prins and colleagues demonstrated the difference in immune cell activation between brain tumor patients responsive and unresponsive to treatment. This work provides novel information that can improve future treatment options for patients with aggressive tumors. It can also better improve treatment strategies for cancers that are likely to metastasize to the brain but have not yet. Overall, the work by Prins and colleagues has the potential to enhance the way scientists and physicians treat cancer patients.  

Article, Robert Prins, David Geffen School of Medicine, UCLA, JCI

About the Author
Master's (MA/MS/Other)
Greetings! I am a predoctoral trainee in the Department of Immunology at Roswell Park Comprehensive Cancer Center. I am passionate about tumor immunology, and hope to one day become an independent principal investigator.
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