Study explains mechanisms behind glioblastoma influence on the immune system

September 12, 2016, Karolinska Institutet

Glioblastomas exert an influence on the microglia, immune cells of the brain, which causes them to stimulate cancer growth rather than attacking it. In a study published in the journal Nature Immunology, an international research team led from Sweden's Karolinska Institutet now explains the molecular mechanisms behind this action.

Glioblastomas are one of the most malignant forms of brain tumour and are difficult to surgically remove because the invade the surrounding healthy brain tissue. Glioblastomas also affect the - of the brain - in such a way that they stimulate the tumour cells instead of attacking them.

The multi-national research group has previously shown that pro-inflammatory activation of microglia is controlled by a group of enzymes called caspases. In the present study, they sought to examine if the way the cancer cells affect microglia also includes similar mechanism. By cultivating microglia and glioblastoma cells together, the researchers were able to show that the inhibit caspase-3 activity in the microglia.

"We show that it's the same inhibition of caspase-3 that causes the microglia to stimulate the tumour cells instead of attacking them," says Bertrand Joseph, Principal Investigator at Karolinska Institutet's Department of Oncology-Pathology. "When we removed caspase-3 from the microglia in a glioblastoma mouse model, the tumours grew more quickly."

According to the study authors, their results demonstrate that the glioma cells use a nitric oxide-dependent mechanism to force microglia to modify caspase-3 to form a tumour-stimulating form of these cells.

"Two things surprised us," says Bertrand Joseph. "First and foremost, that affecting the signalling mechanism between and microglia that we discovered has such a major effect on tumour growth. Secondly, that basal caspase-3 activity, which is often considered to be an absence of activity, fulfills essential function in regulating microglia cell behavior."

Explore further: Breakthrough in understanding of brain development: Immune cell involvement revealed

More information: Glioma-induced inhibition of caspase-3 in microglia promotes a tumor-supportive phenotype, Nature Immunology, DOI: 10.1038/ni.3545

Related Stories

Breakthrough in understanding of brain development: Immune cell involvement revealed

August 25, 2016
Microglia are cells that combat various brain diseases and injuries by swallowing foreign or disruptive objects and releasing molecules that activate repair mechanisms. Recent findings have suggested these brain cells are ...

The brain may show signs of aging earlier than old age

March 18, 2016
A new study published in Physiological Genomics suggests that the brain shows signs of aging earlier than old age. The study found that the microglia cells—the immune cells of the brain—in middle-aged mice already showed ...

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 ...

Immune cells may protect against Alzheimer's

May 19, 2016
Clusters of immune cells in the brain previously associated with Alzheimer's actually protect against the disease by containing the spread of damaging amyloid plaques, a new Yale University School of Medicine study shows.

Blunting brain tumor growth with immune activation

December 8, 2013
Researchers at the University of Calgary's Hotchkiss Brain Institute (HBI) have made a discovery that could lead to better treatment for patients suffering from brain cancer.

Targeting brain cells to alleviate neuropathic pain

August 8, 2016
Neuropathic pain – which affects more than 1 million Americans – could be reduced or even eliminated by targeting brain cells that are supposed to provide immunity but, in some instances, do the opposite, causing chronic ...

Recommended for you

Researchers identify source of molecule linked to nasal polyps, asthma attacks

May 23, 2018
A new discovery about how the immune system responds to common sinus infections and asthma could explain why patients develop these issues in the first place and ultimately may lead to improved targeted therapies. Researchers ...

Study demonstrates new treatment for severe asthma

May 22, 2018
Researchers from McMaster University and the Firestone Institute for Respiratory Health at St. Joseph's Healthcare Hamilton, together with colleagues at other partnering institutions, have developed a new method to treat ...

Eczema drug effective against severe asthma

May 21, 2018
Two new studies of patients with difficult-to-control asthma show that the eczema drug dupilumab alleviates asthma symptoms and improves patients' ability to breathe better than standard therapies. Dupilumab, an injectable ...

Neuron guidance factor found to play a key role in immune cell function

May 21, 2018
Macrophages are white blood cells involved in a variety of biological functions, from destroying infectious pathogens to repairing damaged tissue. To carry out their different roles, macrophages must first be activated and ...

Immune cells hold promise in slowing down ALS

May 21, 2018
Recent research from Houston Methodist Hospital showed that a new immunotherapy was safe for patients with ALS and also revealed surprising results that could bring hope to patients who have this relentlessly progressive ...

First clues to the causes of multiple sclerosis

May 16, 2018
Multiple sclerosis, which affects one in 1,000 people, is frequently characterised by relapses associated with variable functional impairments including among others vision problems, impairment of locomotor functions or difficulties ...

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.