A new study has shed light on why glioblastoma – an aggressive cancer that originates in the brain – doesn’t respond well to immunotherapy, unlike tumours that have spread to the brain from other parts of the body.
Cancer immunotherapy boosts the immune system’s ability to recognise and kill cancer cells. Immune checkpoint blockade is one kind of immunotherapy.
But to date this kind of therapy has not been effective in treating glioblastoma, while it has been shown to slow or even eradicate other types of cancer that metastasise in the brain.
“If we’re going to try to develop new therapies for solid tumours, like glioblastoma, which are not typically responsive, we need to understand the tumour types that are responsive, and learn the mechanisms by which that happens,” says Robert Prins, a professor of molecular and medical pharmacology and of neurosurgery at the University of California Los Angeles, US.
Prins is senior author of the paper published in the Journal of Clinical Investigation.
Immune checkpoints put a brake on the immune response before it can get too strong – which would prevent healthy cells in the body from being destroyed.
This can happen when proteins on the surface of T cells, a type of immune cell, bind to partner proteins on another cell. Sometimes, this is a cancer cell.
Immune checkpoint inhibitor drugs block this from happening, preventing an “off” signal from being sent and allowing the T-cell to go ahead and kill cancer cells.
To do this they studied T cells from 9 people with metastatic brain tumours that had been treated with immune checkpoint blockade and T cells from 19 patients whose metastases hadn’t been treated with immunotherapy. They then compared this with previously published data from 25 recurrent glioblastoma tumours.
“We really were trying to figure out which immune cells are changing in the more responsive tumours in order to better explain the higher response rate to the treatment,” says co-first author Dr Lu Sun, a project scientist at UCLA.
“No study has comprehensively examined the differential effect of immune checkpoint blockade treatment on these two types of brain tumours before.”
Co-author Dr Won Kim, surgical director of UCLA Health’s brain metastasis program, adds: “We found quite a significant difference between the two types of brain tumours and how they respond to immunotherapies.
“There was a tremendous number of T cell lymphocytes that were found within brain metastases following immunotherapy, and while the number of T cell lymphocytes also increased in glioblastoma patients, it wasn’t anywhere near the same extent.”
Before traveling to the brain, T cells must be activated in the lymph nodes by immune cells known as dendritic cells, which share information about the tumour to T cells so they can better attack it. This priming process doesn’t work very effectively when doctors attempt to use immune checkpoint blockade for treating glioblastoma.
Prins concludes that this finding “suggests that enhancing the activation and presentation of T cells by dendritic cells could be a potential treatment strategy.”