Scientists develop potential roadmap for personalized brain cancer treatments

April 8, 2016 by Reggie Kumar

UCLA researchers have developed a promising method to assess how changes in a person's immune response can help predict the effectiveness of a new immunotherapy in people with glioblastoma, the most common and deadly type of brain cancer.

An estimated 18,000 people a year in the U.S. will die from glioblastoma, and the for a GBM patient prescribed a conventional therapy such as surgery, radiation and chemotherapy ranges from 12 to 24 months. The poor outcomes highlight the urgent need for new treatments, and oncologists have so far been unable to predict which GBM patients will likely benefit from immunotherapy.

Led by Drs. Robert Prins and Linda Liau, both UCLA Jonsson Comprehensive Cancer Center members, the two-year study implemented an advanced T-cell receptor sequencing technology to investigate immune responses in GBM patients, before and after being treated with a personalized cellular immune therapy of autologous tumor lysate pulsed dendritic-cell (DC) vaccination.

The team compared the levels of biomarkers on T cells present within tumors and those outside in the bloodstream, and tracked changes throughout treatment. T cells are believed to mediate the effectiveness of the DC-based therapy.

"We performed next generation sequencing of the T cell receptor repertoire on tumors and peripheral blood samples from 15 patients in this study," said Prins, who is an associate professor in the Departments of Neurosurgery and Molecular and Medical Pharmacology at UCLA. "We found that when there were elevated levels of T cells initially present inside the glioblastoma tumor, the patients lived longer following immunotherapy compared to those without T-cell infiltration into their tumors."

When there was a significant overlap of T cells with the same T cell receptors in the tumor and in the blood, survival was also extended, Prins said.

Though this sophisticated technology is just starting to be used in other cancers, the study is the first to utilize high-throughput sequencing to monitor a systemic T-cell response in real-time and examine how T-cell receptor expression in tumors and peripheral blood can be utilized as a potential indicator of a patient's systemic immune response to immune-based treatments.

The scientists plan to conduct further prospective clinical studies with this technology, and then identify specific antigen targets, which may have the potential to improve responses of to immunotherapy.

Explore further: Researchers create a promising new treatment for the deadliest form of brain cancer

More information: M. Hsu et al. TCR sequencing can identify and track glioma-infiltrating T cells after DC vaccination, Cancer Immunology Research (2016). DOI: 10.1158/2326-6066.CIR-15-0240

Related Stories

Researchers create a promising new treatment for the deadliest form of brain cancer

September 2, 2015
UCLA scientists have developed a potentially promising new combination therapy for glioblastoma, the most common and deadliest form of brain cancer.

Genetically engineered immune cell therapy found to boost survival in mice with brain tumors

February 24, 2016
Nagoya University-led research team shows in mice the potential of a special immune cell that targets a key protein in tumor growth that helps stop brain cancer.

Innate immune landscape in glioblastoma patient tumors

February 25, 2016
Glioblastoma is an extremely aggressive brain tumor with limited treatment options. Recent progress in using immunotherapy-based treatment options in other tumor types has spurred interest in developing approaches that might ...

Researchers target specific protein associated with poor survival and treatment

March 4, 2016
Glioblastoma multiforme (GBM) is a highly aggressive brain tumor with low survival rates, with newly diagnosed patients surviving a median of 14 months and recurrent patients surviving a median of only 3 to 9 months. New ...

Team work shines light on how to improve cancer immunotherapy

March 14, 2016
UT Southwestern Medical Center researchers today report on a strategy to make a major advance in cancer treatment even better, and a means to test and refine this new type of immunotherapy.

Histone deacetylase inhibitors enhance immunotherapy in lung cancer models, researchers say

March 31, 2016
Several new immunotherapeutic antibodies that inhibit checkpoint receptors on T cells to restimulate the immune system to target tumors have been approved to treat advanced stage lung cancer and melanoma; however, only 20 ...

Recommended for you

Researchers target undruggable cancers

October 19, 2017
A new approach to targeting key cancer-linked proteins, thought to be 'undruggable," has been discovered through an alliance between industry and academia.

Mutant gene found to fuel cancer-promoting effects of inflammation

October 19, 2017
A human gene called p53, which is commonly known as the "guardian of the genome," is widely known to combat the formation and progression of tumors. Yet, mutant forms of p53 have been linked to more cases of human cancer ...

New study reveals breast cancer cells recycle their own ammonia waste as fuel

October 19, 2017
Breast cancer cells recycle ammonia, a waste byproduct of cell metabolism, and use it as a source of nitrogen to fuel tumor growth, report scientists from Harvard Medical School in the journal Science.

Breast cancer researchers find bacteria imbalance link

October 19, 2017
Researchers in the United States have uncovered differences in the bacterial composition of breast tissue of healthy women versus those with breast cancer.

US regulators approve 2nd gene therapy for blood cancer

October 19, 2017
U.S. regulators on Wednesday approved a second gene therapy for a blood cancer, a one-time, custom-made treatment for aggressive lymphoma in adults.

New findings explain how UV rays trigger skin cancer

October 18, 2017
Melanoma, a cancer of skin pigment cells called melanocytes, will strike an estimated 87,110 people in the U.S. in 2017, according to the Centers for Disease Control and Prevention. A fraction of those melanomas come from ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.