Glioblastoma 'ecosystem' redefined for more effective immunotherapy trials

July 10, 2017
Glioblastoma (histology slide). Credit: Wikipedia/CC BY-SA 3.0

A research team has revealed the intrinsic gene expression patterns of glioblastoma (GBM) tumors, insights that could drive more effective treatments for GBM, the most common and deadly malignant primary brain tumors in adults.

Jackson Laboratory (JAX) Professor Roel Verhaak, Ph.D., is the senior author of a paper published in Cancer Cell showing tumor gene patterns distinct from those of the surrounding immune cells, and characterizing the effects of chemotherapy and radiation treatments.

Verhaak was the first author of a landmark 2010 paper in Cancer Cell that established four subclasses of GBM—proneural, mesenchymal, neural and classical—based on found in patient tumors. That paper has been widely influential in the research world, yet, observes Verhaak, "these four subtypes have not translated into differential strategies. Every glioblastoma patient receives essentially the same treatment. We hope that our latest work will improve understanding of how to optimally stratify patients, another step towards precision medicine and more targeted, effective treatments."

The cells that surround a tumor are known as its microenvironment, usually consisting of , supporting cells and other normal cells. Tumors donated to tissue banks consist of a mixture of microenvironment cells, cancer cells and the surgeon's narrow margin of safety to ensure the removal of cancerous tissue while avoiding damaging essential brain functions.

In the new paper, the research team isolated the intrinsic gene expression of GBM tumors from the contributions by the tumor microenvironment, and observed the impact by the standard cancer treatment regimens of temozolomide and radiation on that expression, as well as subtracting out the effects of therapy on the tumor-associated non-cancer cells.

"By separating out the contributions of the microenvironment, we developed a much clearer picture of the 'ecosystem' of hundreds of tumors," Verhaak says. "We determined what types of cells are in the microenvironment and what their contributions are, and also assessed how treatment affects the microenvironment as well as the themselves."

(Through this approach, the researchers found that the molecular markers defining the neural subtype of GBM could be ascsribed to the presence of normal neural tissue in the margin, thus not representing a true subtype.)

By studying in glioblastomas after treatment, their analysis also revealed that the presence of macrophages correlates with poorer outcomes for GBM patients receiving radiation therapy, and that tumors with a relatively high number of point mutations have an increased number of positive T , indicating they could respond to a kind of immunotherapy known as checkpoint inhibitors.

The resulting gene expression datasets, which are publicly available to researchers, provide comprehensive profiles of glioblastoma characteristics to more accurately guide immunotherapy trials.

Explore further: Single-cell RNA sequencing reveals detailed composition of two major types of brain tumor

More information: Wang et al.: Tumor evolution of glioma intrinsic gene expression subtype associates with immunological changes in the microenvironment. Cancer Cell, DOI: 10.1016/j.ccell.2017.06.003

Related Stories

Single-cell RNA sequencing reveals detailed composition of two major types of brain tumor

March 30, 2017
Detailed analysis of two brain tumor subtypes has revealed that they may originate from the same type of neural progenitor cells and be distinguished by gene mutation patterns and by the composition of their microenvironments. ...

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 ...

Tumor immune fitness determines survival of lung cancer patients

June 19, 2017
In recent years, immunotherapy, a new form of cancer therapy that rouses the immune system to attack tumor cells, has captivated the public's imagination. When it works, the results are breathtaking. But more often than not ...

New study: Aggressive breast cancer grows faster in obese environment

March 31, 2017
It's not just what's inside breast cancer cells that matters. It's also the environment surrounding cancer cells that drives the disease, according to researchers at the University of North Carolina Lineberger Comprehensive ...

Silencing cancer cell communication may reduce the growth of tumors

January 30, 2017
In several types of cancer, elevated expression of the chemokine receptor CCR4 in tumors is associated with poor patient outcomes. Communication through CCR4 may be one mechanism that cancer cells use to create a pro-tumor ...

Researchers use new computational method to define immune cell interactions

March 15, 2017
Immunotherapy, harnessing a patient's immune system to help fight cancer, has shown much promise as a potential cancer treatment. In a newly published study, a research team at Dartmouth-Hitchcock's Norris Cotton Cancer Center ...

Recommended for you

'Labyrinth' chip could help monitor aggressive cancer stem cells

September 21, 2017
Inspired by the Labyrinth of Greek mythology, a new chip etched with fluid channels sends blood samples through a hydrodynamic maze to separate out rare circulating cancer cells into a relatively clean stream for analysis. ...

Whole food diet may help prevent colon cancer, other chronic conditions

September 21, 2017
A diet that includes plenty of colorful vegetables and fruits may contain compounds that can stop colon cancer and inflammatory bowel diseases in pigs, according to an international team of researchers. Understanding how ...

New kinase detection method helps identify targets for developing cancer drugs

September 21, 2017
Purdue University researchers have developed a high-throughput method for matching kinases to the proteins they phosphorylate, speeding the ability to identify multiple potential cancer drug targets.

Drug combination may improve impact of immunotherapy in head and neck cancer

September 21, 2017
Checkpoint inhibitor-based immunotherapy has been shown to be very effective in recurrent and metastatic head and neck cancer but only in a minority of patients. University of California San Diego School of Medicine researchers ...

Poliovirus therapy induces immune responses against cancer

September 20, 2017
An investigational therapy using modified poliovirus to attack cancer tumors appears to unleash the body's own capacity to fight malignancies by activating an inflammation process that counter's the ability of cancer cells ...

Brain cancer growth halted by absence of protein, study finds

September 20, 2017
The growth of certain aggressive brain tumors can be halted by cutting off their access to a signaling molecule produced by the brain's nerve cells, according to a new study by researchers at the Stanford University School ...

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.