Study could help explain why certain brain tumors don’t respond well to immunotherapy

A study led by researchers at the UCLA Jonsson Comprehensive Cancer Center sheds new light on why tumors that have spread to the brain from other parts of the body respond to immunotherapy while glioblastoma, an aggressive cancer that originates in the brain, does not.

In people with tumors that originated in other parts of the body but spread to the brain, treatment with a type of immunotherapy called immune checkpoint blockade appears to elicit a significant increase in both active and exhausted T cells — signs that the T cells have been triggered to fight the cancer. The reason the same thing doesn't occur in people with glioblastoma is that anti-tumor immune responses are best initiated in draining lymph nodes outside of the brain, and that process does not occur very effectively in glioblastoma cases.

To date, immunotherapy has not been effective in treating glioblastoma, but it has been shown to slow or even eradicate other types of cancer, such as melanoma, which frequently metastasizes to the brain.

The new research, published in the Journal of Clinical Investigation, could help improve the effectiveness of immunotherapy for people with brain tumors and it could suggest new paths in the effort to help develop more effective therapies.

If we’re going to try to develop new therapies for solid tumors, like glioblastoma, which are not typically responsive, we need to understand the tumor types that are responsive, and learn the mechanisms by which that happens.
Study’s senior author, Robert Prins, a professor of molecular and medical pharmacology and of neurosurgery at the David Geffen School of Medicine at UCLA.
We found quite a significant difference between the two types of brain tumors 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.
Study author Dr. Won Kim, surgical director of UCLA Health’s brain metastasis program and a member of the Jonsson Cancer Center.

Prins, who is also a researcher at the Jonsson Cancer Center, said that finding “suggests that enhancing the activation and presentation of T cells by dendritic cells could be a potential treatment strategy.”


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