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Abstract: Glioblastoma remains profoundly resistant to current immunotherapeutic strategies

Here, Fanghui Lu & team report OLIG2, a master transcription factor in glioblastoma stem cells, enables immune evasion by suppressing CXCL10. And, targeting OLIG2 overcomes immunotherapy resistance and improves survival.


1Department of Cancer Center, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.

2Department of Neurosurgery, Key Laboratory of Major Brain Disease and Aging Research (Ministry of Education), The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

3School of Basic Medical Sciences, Chongqing Medical University, Chongqing, China.

New cellular immunotherapy approach for Alzheimer’s disease

Alzheimer’s disease starts with a sticky protein called amyloid beta that builds up into plaques in the brain, setting off a chain of events that results in brain atrophy and cognitive decline. Microglia, immune cells that reside in the brain, are responsible for removing brain waste but can become dysfunctional when overwhelmed in the context of neurodegenerative disease.

To reduce the cleaning burden on microglia, first author transformed astrocytes, the most abundant cell type in the brain, into amyloid-cleaning machines. The author custom-designed and delivered a gene to astrocytes that codes for the chimeric antigen receptor (CAR) via a harmless virus injected into mice. The CAR, now present on the surface of astrocytes, enabled the cells to capture and engulf amyloid beta proteins. With their newly acquired ability, the astrocytes — generally responsible for keeping the brain tidy — concentrated their efforts on only cleaning amyloid beta plaques in mice prone to its buildup.

Mice carrying genetic mutations that increase people’s risk of developing Alzheimer’s disease develop amyloid beta plaques that saturate the brain by six months of age. The author injected two groups of mice with the virus carrying the CAR-expressing gene: young mice before they developed plaques and older mice with brains saturated with plaques, then, waited three months.

As the younger mice aged, the CAR-astrocytes prevented amyloid beta plaque development. At nearly six months of age, when untreated mice normally have brains saturated with harmful plaques, brains of treated mice were plaque-free. Meanwhile, older mice with plaque-saturated brains at the time of treatment saw a 50% reduction in the amount of amyloid beta plaques compared to mice receiving an injection of a virus lacking the CAR gene.

The researchers have filed a patent related to the approach used to engineer CAR-astrocytes.

“Consistent with the antibody drug treatments, this new CAR-astrocyte immunotherapy is more effective when given in the earlier stages of the disease,” said a co-author on the paper. “But where it differs, and where it could make a difference in clinical care, is in the single injection that successfully reduced the amount of harmful brain proteins in mice.” ScienceMission sciencenewshighlights.


Neural crest gene regulatory networks as drivers of development, diversification and disease

Neural crest cells (NCCs) are multipotent stem cells whose activation, migration and diversification are tightly controlled by gene regulatory networks that shape NCC function in vertebrate development, evolution, tissue repair and disease.

Genetic factors drive the link between cognitive ability and socioeconomic status

A new study of German twins suggests that the strong connection between a young adult’s cognitive ability and their future socioeconomic status is largely driven by their genes, rather than shared family environments or random life events.

Your gut microbes can be anti-aging—scientists are uncovering how to keep your microbiome youthful

People have long given up on the search for the Fountain of Youth, a mythical spring that could reverse aging. But for some scientists, the hunt has not ended—it’s just moved to a different place. These modern-day Ponce de Leóns are investigating whether gut microbes hold the secret to aging well.

The gut microbiome refers to the vast collection of microscopic organisms—bacteria, fungi, and viruses—that largely inhabit the colon. These microbes aid in digestion and produce molecules that affect your physiology and psychology. The composition of the microbiome is influenced by a combination of factors, including genetics, diet, the environment, medications, and age.

I’m a microbiology professor and author of “Pleased to Meet Me: Genes, Germs and the Curious Forces That Make Us Who We Are,” which describes how the gut microbiome contributes to physical and mental health. The discovery that the gut microbiome changes with age has ignited studies to determine whether the Fountain of Youth might be right under your nose, down inside your gut.

PV inhibitory neurons, not overall prefrontal cortex decline, linked to cocaine-seeking relapse

Drug addiction carries an extremely high risk of relapse, as cravings can be reignited by minor stimuli even long after one has stopped using. Previously, this phenomenon was attributed to a decline in the function of the prefrontal cortex (PFC), which regulates impulses. However, a joint international research team has recently revealed that the cause of addiction relapse is not a simple decline in brain function, but rather an imbalance in specific neural circuits.

Why anger feels close to fear: Brain charts emotion in a map-like way

It is well established in psychology that humans conceptualize emotions by features known as valence (the degree of pleasantness or unpleasantness) and arousal (the intensity of bodily reactions, such as rapid breathing or a racing heart).

If you think of “pleasantness” as longitude and “bodily reaction” as latitude, you can imagine a “mental map,” with nodes that “chart” knowledge of emotion.

The neural mechanisms giving rise to this configuration, however, have remained unclear.

Focused ultrasound subtly primes human brain to respond, EEG study finds

A research team at Carnegie Mellon University has developed a new noninvasive brain stimulation technique, by showing how focused ultrasound affects the human brain. Using brainwave recordings from human participants, the team found that focused ultrasound can subtly influence brain activity without directly causing neurons to fire. The work clarifies conflicting results in the field and introduces a new approach to noninvasive brain stimulation. The study is published in Nature Communications.

Focused ultrasound has been studied for years, but its effects in humans are not well understood. One challenge is that the technology makes a quiet beeping sound that can trigger hearing pathways in the brain, making it hard to know whether changes are caused by the sound or by the ultrasound itself. Previous studies using MRI scans may also produce misleading signals.

To address these limitations, researchers conducted a resting-state study in 27 human participants using concurrent whole-brain EEG recordings. They compared low-intensity transcranial focused ultrasound (tFUS) alone, a mild electrical brain stimulation called tDCS, and a new approach that combines the two, deemed transcranial electro-acoustic stimulation (tEAS). When used alone, neither ultrasound nor electrical stimulation caused clear, targeted brain responses. However, when combined, they produced strong, specific activity in the targeted area.

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