Cracking the Code: Unraveling Why Some Brain Tumors Resist Immunotherapy

Study Reveals Why Some Brain Tumors Respond to Immunotherapy

Scientists at UCLA Jonsson Comprehensive Cancer Center have discovered why certain brain tumors react to immunotherapy differently. This research offers new insights into why tumors that spread to the brain from other parts of the body respond to immunotherapy, while a type of aggressive brain cancer called glioblastoma does not.

When tumors from other parts of the body spread to the brain, a type of immunotherapy called immune checkpoint blockade seems to activate both active and exhausted T cells. These T cells show that the body is trying to fight the cancer. However, this reaction doesn’t happen the same way in glioblastoma patients because the immune responses that work well against tumors usually start in lymph nodes outside the brain, and this process doesn’t work very effectively for glioblastoma.

So far, immunotherapy hasn’t been successful in treating glioblastoma, but it has shown promise in slowing down or getting rid of other cancers, like melanoma, which often spreads to the brain.

The new research, published in the Journal of Clinical Investigation, could help make immunotherapy better for people with brain tumors and could also suggest new ways to develop more effective treatments.

“We need to understand why some tumors respond in order to develop new treatments, especially for tough ones like glioblastoma,” explained Robert Prins, a professor at the David Geffen School of Medicine at UCLA, who led the study.

The researchers looked at immune cells from nine people with brain tumors that had spread and were treated with immune checkpoint blockade. They compared these cells to immune cells from 19 patients with brain metastases who didn’t receive this type of treatment.

Using a method called single-cell RNA sequencing, they looked at the genetic material in both sets of cells and compared it to information from previous studies about recurrent glioblastoma tumors. This helped them understand how the immunotherapy affected T cells.

“We wanted to find out which immune cells change in tumors that respond well to treatment, so we can understand why it works better in those cases,” said Lu Sun, one of the co-first authors of the study.

In tumors that had spread to the brain, the researchers saw that the T cells had specific traits that help fight tumors in the brain. This might be because these T cells were better prepared outside of the brain.

Before going to the brain, T cells get activated in the lymph nodes. During this process, a type of immune cells called dendritic cells tell T cells about the tumor, so they can fight it better. However, this process doesn’t work as well when doctors use immunotherapy for glioblastoma treatment.

The researchers also found a specific group of exhausted T cells that were linked to longer survival in people with brain-metastasized cancer.

“We saw a big difference in how the two types of brain tumors respond to immunotherapy,” said Dr. Won Kim, another study author.

This discovery suggests that improving the activation of T cells by dendritic cells could be a way to treat brain tumors in the future.

In their next studies, the researchers plan to analyze data from more people diagnosed with melanoma that has spread to the brain.

The study’s other co-first author, Jenny Kienzler, conducted the research while at UCLA. The research was supported by grants from organizations like the National Institutes of Health and the Brain Tumor Funder’s Collaborative.

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