Which glioblastoma patients will respond to immunotherapy?

Northwestern Medicine scientists have discovered a new biomarker to identify which patients with brain tumors called glioblastomas — the most common and malignant of primary brain tumors — might benefit from immunotherapy.

The treatment could extend survival for an estimated 20% to 30% of patients. Currently, patients with glioblastoma do not receive this life-prolonging treatment because it has not been fully understood which of them could benefit.

“This is an important breakthrough for patients who have not had an effective treatment in the cancer drug arsenal available to them,” said Dr. Adam Sonabend, the senior/corresponding author of this study, and associate professor of neurosurgery at Northwestern University Feinberg School of Medicine and a Northwestern Medicine brain-tumor neurosurgeon. “It might ultimately influence the decision on how to treat glioblastoma patients and which patients should get these drugs to prolong their survival.”

“Our study emphasizes important immune cells that might be relevant for response to immunotherapy. We hope that ultimately this benefits glioblastoma patients,” said Victor Arrieta, a post-doctoral scientist at the Sonabend lab and the first author of this study.

The immunotherapy response marker now needs to be validated in a clinical trial to make sure the study findings are reproducible and applicable to any glioblastoma patient, Sonabend said. He also is a member of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University.

The study was published in Nature Cancer Nov. 29.

Glioblastomas are the most common form of malignant brain tumors in adults and have the worst prognosis. Patients are treated with radiation and chemotherapy, but the cancer inevitably recurs. Upon recurrence, there are no treatments that prolong survival.

How T Cells recognize infection or disease

Research illuminating an elusive component of the adaptive immune system,
how gamma delta T cells sense the metabolite-antigen presenting molecule MR1.
Artwork image created by Dr Erica Tandori. 

Monash University researchers have expanded their knowledge of how T cells might recognize infections or disease, providing key insight into how an often-overlooked T cell lineage becomes activated when encountering pathogens such as viruses, bacteria, and cancers.

T cells communicate with other cells in the body in search of infections or diseases. This crosstalk relies on specialized receptors known as T cell receptors that recognize foreign molecular fragments from an infection or cancer that are presented for detection by particular molecules called major histocompatibility complex (MHC) or MHC-like.

In this study, Monash Biomedicine Discovery Institute scientists have expanded the understanding of how a poorly defined class of gamma delta T cells recognizes an MHC-like molecule known as MR1. MR1 is a protein sensor that takes cellular products generated during infections or disease and presents them for T cells to detect, thereby alerting the immune system.

These gamma delta T cells play an understudied role within specific tissues around the body including the intestinal tract and may be an important factor in diseases that impact these tissues.

The findings are published today in the Proceedings of the National Academy of Sciences.

The study was co-led by Dr Benjamin S. Gully and Dr Martin Davey with first author Mr Michael Rice from the Monash Biomedicine Discovery Institute.

Closest pair of supermassive black holes yet

Hi-Res Zoomable Left Image | Hi-Res Zoomable Right Image
This image shows close-up (left) and wide (right) views of the two bright galactic nuclei, each housing a supermassive black hole, in NGC 7727, a galaxy located 89 million light-years away from Earth in the constellation Aquarius. Each nucleus consists of a dense group of stars with a supermassive black hole at its center. The two black holes are on a collision course and form the closest pair of supermassive black holes found to date. It is also the pair with the smallest separation between two supermassive black holes found to date — observed to be just 1600 light-years apart in the sky.    The image on the left was taken with the MUSE instrument on ESO’s Very Large Telescope (VLT) at the Paranal Observatory in Chile while the one on the right was taken with ESO's VLT Survey Telescope.  Credit: ESO/Voggel et al.; ESO/VST ATLAS team.
Acknowledgement: Durham University/CASU/WFAU

Using the European Southern Observatory’s Very Large Telescope (ESO’s VLT), astronomers have revealed the closest pair of supermassive black holes to Earth ever observed. The two objects also have a much smaller separation than any other previously spotted pair of supermassive black holes and will eventually merge into one giant black hole.

Located in the galaxy NGC 7727 in the constellation Aquarius, the supermassive black hole pair is about 89 million light-years away from Earth. Although this may seem distant, it beats the previous record of 470 million light-years by quite some margin, making the newfound supermassive black hole pair the closest to us yet.

Team Builds First Living Robots That Can Reproduce

To persist, life must reproduce. Over billions of years, organisms have evolved many ways of replicating, from budding plants to sexual animals to invading viruses.

Now scientists have discovered an entirely new form of biological reproduction — and applied their discovery to create the first-ever, self-replicating living robots.

The same team that built the first living robots ("Xenobots,” assembled from frog cells — reported in 2020) has discovered that these computer-designed and hand-assembled organisms can swim out into their tiny dish, find single cells, gather hundreds of them together, and assemble “baby” Xenobots inside their Pac-Man-shaped “mouth” — that, a few days later, become new Xenobots that look and move just like themselves.

And then these new Xenobots can go out, find cells, and build copies of themselves. Again and again.

“With the right design — they will spontaneously self-replicate,” says Joshua Bongard, a computer scientist and robotics expert at the University of Vermont who co-led the new research.

The results of the new research were published November 29, 2021, in the Proceedings of the National Academy of Sciences.

Bots talk like humans but their cloned personalities give them away

The image indicates the amount of genuine human accounts (blue) and fake bot accounts (red) by different ages and personality scores within the data of the study. The bot accounts have reasonable ages and personalities but only within an extremely thin range of values (ie, they all express the same human attributes), while the genuine human accounts have a large spread of values.
Credit: Stony Brook University

Social Bots, or accounts from non-genuine people, are posted all over social media. They infiltrate popular topics and serious ones like the Covid-19 pandemic. These bots are not like obvious robocalls or spam emails. They are designed to be human-like and interact with real social media users without their awareness. In fact, recent studies show that social media users find them mostly indistinguishable from real humans.

Now a study by Stony Brook University and University of Pennsylvania researchers published in Findings of the Association for Computational Linguistics (ACL) attempts to look at how human these social spambots really are by estimating 17 human attributes of the bot and implementing state-of-the-art machine learning and natural language processing. The study findings shed light on how bots behave on social media platforms and interact with genuine accounts, as well as the capabilities of current bot-generation technologies.

“This research gives us insight into how bots are able to engage with these platforms undetected,” explains lead author Salvatore Giorgi, a Visiting Scholar at Stony Brook University and a PhD student in the Department of Computer and Information Science (CIS) at the University of Pennsylvania’s School of Engineering and Applied Sciences. “If a Twitter user thinks an account is human, then they may be more likely to engage with that account. Depending on the bot’s intent, the end result of this interaction could be innocuous, but it could also lead to engaging with potentially dangerous misinformation.”

The superfoods that fueled ancient Andeans through 2,500 years of turmoil

Quinoa growing on Bolivia’s Taraco Peninsula
Photo by Maria Bruno

What if Indigenous diets could save our politically and ecologically strained planet? The answer may lie in the success of an ancient civilization high in the Andes Mountains, where not much grows.

UC Berkeley archaeologists reconstructed the diets of ancient Andeans living around Lake Titicaca, which straddles Bolivia and Peru 12,500 feet above sea level. They found that quinoa, potatoes and llama meat helped fuel the Tiwanaku civilization through 2,500 years of political and climate upheaval.

The findings, appearing this week in the Proceedings of the National Academy of Sciences journal, help explain the endurance of Andean cultural practices in the millennia preceding the Inca Empire. Moreover, they underscore the contribution of traditional Indigenous foods to human resilience.

“Thousands of years ago, these people already knew that quinoa was a superfood. They came up with this lucky triangle to meet their dietary needs in a pretty stark environment, and we can learn something from them,” said study senior author Christine Hastorf, a UC Berkeley professor of anthropology.

“Today, we’re living under the cloud of climate change. Rising sea levels are drowning tiny Pacific islands, and droughts and wildfires are destroying California’s crops,” she added. “Our findings point to how ancient people successfully adjusted to environmental and political changes, bolstered by a healthy Indigenous diet.”

FDA approves pioneering drug for ovarian cancer surgery

Ovarian cancer patient Carol Giandonato admits to being apprehensive when her oncologist told her he wanted to make her cancer cells turn fluorescent green.

"Am I going to glow in the dark? Will I be green?" she asked him.

Her surgeon explained that when viewing the cancer site, the cancerous lesions would be illuminated with near-infrared light during surgery.

Using this approach, her surgeon was able to find a hidden tumor that would have otherwise gone undetected. Giandonato was one of the first patients for a new drug designed to help surgeons find ovarian cancer tumors and cells — that imaging agent was just approved Monday (November 29) by the U.S. Food and Drug Administration.

The drug will be released with the brand name Cytalux. It was invented at Purdue University and will be released by On Target Laboratories.

The imaging agent is delivered via an IV injection between one and nine hours before the surgery for ovarian cancer. The fluorescent imaging agent binds to the cancer cells, allowing surgeons to find additional tumors in 27% of the patients, which would have otherwise been left behind, according to results of the Phase 3 clinical trial.

Pesticides Can Affect Multiple Generations of Bees

The blue orchard bee, shown here on the lacy phacelia wildflower,
was exposed to a neonicotinoid for the study.
Credit: Clara Stuligross/UC Davis

A new study from researchers at the University of California, Davis, finds that pesticides not only directly affect bee health, but effects from past exposure can carry over to future generations. The study, published in the journal Proceedings of the National Academy of Sciences, suggests that bees may require multiple generations to recover from even a single application.

Bees play a critical role in agricultural ecosystems, providing pollination for many important crops. In most agricultural areas, bees may be exposed to pesticides multiple times, over multiple years. Studies to date have only looked at exposure to pesticides in one life stage or over one year.

“It was important for us to understand how exposure persists from one generation to the next,” said lead author Clara Stuligross, a Ph.D. candidate in ecology at UC Davis. “Our findings suggest we need to be doing more to help mitigate risks or we limit critical pollination services.”

Rhythms of the krill

Diffuse sunlight, moonlight, aurora, and artificial light can all be seen during the Arctic Polar night, including near Kongsfjorden, Svalbard. Svalbard is an archipelago northeast of Greenland. When it is lightest in the Arctic polar night, usually around the middle of the day known as midday twilight, Arctic krill (inset) know to swim down to the bottom in order to hide from predators. When it is darkest in the Arctic polar night, they swim to the surface in search of bioluminescent food.

Photo by Geir Johnsen Photo illustration inset by Tammy Beeson

Around 11:30 a.m. or so, you might find yourself hankering for lunch. The reason for this is that our biological rhythms are trained to tell ourselves when we are hungry, and when we do get that craving, our bodies know that it’s time to eat. The same is true for visual rhythms.

During the day, it is typically lighter than at night. Because of this, our visual system changes so that it can be ready to work under brighter light conditions. During the night time, our eyes become more sensitive to adjust to the lack of light available.

It turns out that the same thing happens for Arctic krill. When it is lightest in the Arctic polar night — a time of year at high latitudes when the sun remains below the horizon for the entire 24-hour period — usually around the middle of the day known as midday twilight, the Arctic krill know to swim down to the bottom in order to hide from predators. When it is darkest in the Arctic polar night, that’s when they swim to the surface in search of bioluminescent food.

A new study published in the PLOS Biology Research Journal looked at this visual sensitivity rhythm in Arctic krill during the Arctic polar night.

New cancer therapy from Yibin Kang’s lab

Yibin Kang
Photo by Denise Applewhite, Office of Communications

Imagine you could cure cancer by targeting one tiny gene. Imagine that same gene occurred in every major cancer, including breast, prostate, lung, liver and colon. Imagine that the gene is not essential for healthy activity, so you could attack it with few or no negative side effects.

Cancer biologist Yibin Kang has spent more than 15 years investigating a little-known but deadly gene called MTDH, or metadherin, which enables cancer in two important ways — and which he can now disable, in mice and in human tissue, with a targeted experimental treatment that will be ready for human trials in a few years. His work appears in two papers in today’s issue of Nature Cancer (Paper One, Paper Two).

“You can’t find a drug target better than this: MTDH is important for most major human cancers, not important for normal cells, and it can be eliminated with no obvious side effects,” said Kang, Princeton’s Warner-Lambert/Parke-Davis Professor of Molecular Biology and one of the principal investigators of the Princeton Branch of the Ludwig Institute for Cancer Research.

“In the two papers we are publishing back-to-back today, we identify a compound, show it is effective against cancer, and show that it is very, very effective when combined with chemotherapy and immunotherapy,” said Kang. “Even though metastatic cancers are scary, by figuring out how they work — figuring out their dependency on certain key pathways like MTDH — we can attack them and make them susceptible to treatment.”

For years, Kang has focused on metastasis — the term for cancer’s ability to spread from one place to another in the body — because he knows that metastasis makes cancer deadly. While 99% of breast cancer patients survive five years after diagnosis, only 29% do if the cancer has metastasized, according to current numbers from the National Cancer Institute.