Research Roundup: “Bad Fat” Slows Killer T-Cells from Attacking Cancer and More
Every week there are numerous scientific studies published. Here’s a look at some of the more interesting ones.
“Bad Fat” Slows Killer T-Cells from Attacking Cancer
Researchers at the Salk Institute discovered that the environment inside tumors, otherwise called the tumor microenvironment, contains a lot of oxidized fat molecules. When they are ingested by killer T-cells, this “bad fat” suppresses the killer T-cells’ ability to kill cancer cells. The T-cells, requiring energy, increase the amount of a cellular fat transporter, CD36, which then saturates the T-cells with more oxidized fat, which further decreases their tumor-killing ability. The research was published in the journal Immunity.
“We know that tumors are a metabolically hostile environment for healthy cells, but elucidating which metabolic processes are altered and how this suppresses immune cell function is an important area of cancer research that is gaining a lot of attention,” said Susan Kaech, senior author and director of Salk’s NOMIS Center for Immunobiology and Microbial Pathogenesis. “Our findings uncovered a novel mode of immunosuppression in tumors involving the import of oxidized fats (AKA lipids) in T-cells via the cellular fat transporter CD36, which impairs their anti-tumor functions locally.”
This type of lipid oxidation not only happens in T-cells, but also in tumor cells. If it increases in tumor cells, it can result in cell death. This has resulted in excitement in cancer research to increase lipid oxidation in tumor cells to a lethal level, but Kaech and her team’s research suggests this should be approached cautiously.
“Now that we’ve uncovered this vulnerability of T-cells to lipid oxidation stress, we may need to find more selective approaches to inducing lipid oxidation in the tumor cells but not in the T-cells,” Kaech said. “Otherwise, we may destroy the anti-tumor T-cells in the process, and our work shows a few interesting possibilities for how to do this.”
New Drug Target for ALS
Investigators out of Boston Children's Hospital confirmed two known drug targets and identified an existing class of drugs as potential novel treatments for amyotrophic lateral sclerosis (ALS). Working in collaboration with Pfizer, the group created motor neurons used for drug screening by utilizing induced pluripotent stem cells from tissue samples of ALS patients who carried the SOD1(A4V) mutation. They developed a high-throughput, live-cell imaging system to measure the motor neurons’ excessive firing before and after exposure to candidate drugs. They had previously demonstrated that human motor neurons with ALS mutations are more excitable than normal motor neurons. The two classes were AMPA receptors and Kv7 potassium channels, which they confirmed. A company, QurAlis, co-founded by the Boston researchers, is developing the drugs for ALS. The new class of candidate drugs are agonists to the dopamine D2 receptor (DRD2), which had not been identified before as being involved in motor neuron hyperexcitability. Some DRD2 agonists, such as bromocriptine and sumanirole are commercially available.
New Glial Cells Discovered in the Brain
Investigators with the University of Basel discovered two new types of glial cells in the brain. Glial cells are a type of immune and support cells. They believe these glial cells may play an important role in brain plasticity and repair. The researchers identified a molecular signal that stimulated stem cells from their quiescent state, which allowed them to locate multiple domains that created glial cells in this stem cell reservoir. Basically, they discovered an activation switch for quiescent stem cells.
Brain Cell Lipids May Play Role in Alzheimer’s Progression
Researchers with Aarhus University in Denmark published research on the role of brain cell membrane lipids and their role in regulating C99, a protein within the amyloid pathway. They believe this plays a significant role in the progression of Alzheimer’s disease. Toxic amyloid plaques, which are central to Alzheimer’s disease, are formed from several enzymes that cleave the APP protein. The APP protein lies within the neuronal cell membrane. When the APP protein is cleaved, it forms C99, which is eventually cleaved to release the beta-amyloid peptide that can become plaques. The two proteins, C99 and APP, protect themselves from being cleaved by forming homodimers, a protein made up of two identical polypeptide chains. The C99 molecule interactions are regulated by lipids that make up the membrane where the protein is located.
Weak Brain Waves Might Warn of Age-Related Neurodegeneration
Scientists conducted a study suggesting that weakened electrical signals in the brain might warn of age-related neurodegenerative diseases such as Alzheimer’s. They used electroencephalography to measure electrical activity in the patient’ brains while they viewed black and white patterns on a screen. These types of patterns are known to cause gamma oscillations in the part of the brain that processes visual information. They also monitored eye movements. People who had been diagnosed with mild cognitive impairment or Alzheimer’s disease had weaker gamma waves compared to healthy individuals of the same age.
First author Murty Dinavahi, who was a Ph.D. Research Scholar at the Centre for Neuroscience, Indian Institute of Science, Bengaluru, India, at the time of the study, but now is a Postdoctoral Associate at the University of Maryland, says, “As tools for detecting Alzheimer’s disease early are limited, there is a need to develop a reliable, non-invasive test that would enable early diagnosis.”
Sleep Study Suggests Dreams Reflect Multiple Memories and Anticipate Future Events
Researchers with Furman University in Greenville, South Carolina, conducted a study in 48 students using polysomnography. The participants were awakened up to 13 times to report on their experiences during sleep onset, REM sleep, and non-REM sleep. The next morning, they identified and described waking life sources for each dream reported. A total of 481 reports were analyzed. They found that 53.5% of dreams were associated with a memory, and almost 50% said the memory source was linked to multiple past experiences. Of them, 25.7% were related to specific impending events, and 37.4% with a future event source were related to one or more specific memories of past experiences. And the later in the night the dreams occurred, the more likely they were to be oriented toward the future.
“Humans have struggled to understand the meaning of dreams for millennia,” said principal investigator Erin Wamsley, associate professor in the department of psychology and program in neuroscience at Furman University. “We present new evidence that dreams reflect a memory-processing function. Although it has long been known that dreams incorporate fragments of past experience, our data suggest that dreams also anticipate probable future events.”