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Brain Tumor

Unlocking Lung Cancer Treatment: Discovery of Master Regulator Blocks Immunotherapy Response

Researchers have discovered that ‘DEAD-box helicases 54 (DDX54)’, a type of RNA-binding protein, is the master regulator that hinders the effectiveness of immunotherapy — opening a new path for lung cancer treatment.

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Unlocking Lung Cancer Treatment: Discovery of Master Regulator Blocks Immunotherapy Response

Lung cancer is one of the most aggressive types of cancer, accounting for a significant number of cancer-related deaths worldwide. Despite advances in treatment options like immunotherapy, fewer than 20% of patients respond to these treatments. This highlights the urgent need for new strategies tailored to both responders and non-responders.

Researchers at KAIST have made a groundbreaking discovery that sheds light on this issue. They identified ‘DEAD-box helicases 54 (DDX54)’, a type of RNA-binding protein, as the master regulator that hinders the effectiveness of immunotherapy. This breakthrough technology has been transferred to faculty startup BioRevert Inc., where it is currently being developed as a companion therapeutic and expected to enter clinical trials by 2028.

The research team led by Professor Kwang-Hyun Cho from the Department of Bio and Brain Engineering demonstrated that suppressing DDX54 enhances immune cell infiltration into tumors and significantly improves the efficacy of immunotherapy. This study is especially significant in that it successfully demonstrated that suppressing DDX54 in immune-desert lung tumors can overcome immunotherapy resistance and improve treatment outcomes.

The team used transcriptomic and genomic data from immune-evasive lung cancer patients to infer gene regulatory networks through systems biology techniques. They identified DDX54 as a central regulator in the immune evasion of lung cancer cells. In a syngeneic mouse model, the suppression of DDX54 led to significant increases in the infiltration of anti-cancer immune cells such as T cells and NK cells, and greatly improved the response to immunotherapy.

Single-cell transcriptomic and spatial transcriptomic analyses further showed that combination therapy targeting DDX54 promoted the differentiation of T cells and memory T cells that suppress tumors, while reducing the infiltration of regulatory T cells and exhausted T cells that support tumor growth. The mechanism is believed to involve DDX54 suppression inactivating signaling pathways such as JAK-STAT, MYC, and NF-κB, thereby downregulating immune-evasive proteins CD38 and CD47.

This discovery has significant implications for lung cancer treatment. By targeting the master regulator DDX54, clinicians can induce responsiveness to immunotherapy in previously resistant cancers, ultimately improving treatment outcomes for patients.

The study was published in the Proceedings of the National Academy of Sciences of the United States of America (PNAS) on April 2, 2025, with Jeong-Ryeol Gong being the first author, Jungeun Lee a co-first author, and Younghyun Han a co-author of the article. This work was supported by the Ministry of Science and ICT and the National Research Foundation of Korea through the Mid-Career Research Program and Basic Research Laboratory Program.

Brain Tumor

“Revolutionizing Lymphoma Treatment: Enhanced CAR T Cell Therapy Shows Promise in Small Study”

A phase I study of a next-generation CAR T cell therapy showed a 52 percent complete remission rate for patients with relapsed/refractory lymphoma.

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The article describes a groundbreaking study that has shown promising results in treating lymphoma patients who have resisted multiple rounds of other cancer treatments, including commercially available CAR T cell therapies. The new enhanced CAR T cell therapy, dubbed huCART19-IL18, was found to be highly effective in 81% of patients and resulted in complete remission in 52%. This is a significant improvement over traditional CAR T cell therapies, which have been shown to result in long-term remission in only around 50% of patients.

The study, led by researchers at the University of Pennsylvania, used a new process that shortens the manufacturing time for the CAR T cells to just three days. This means that patients with aggressive, fast-growing cancers can begin CAR T cell therapy quicker than is currently possible with standard manufacturing times of nine to 14 days.

The addition of interleukin 18 (IL18) to the CAR T cells enhanced their ability to attack cancer cells and protected them from immune suppression and T cell exhaustion. The researchers also found that the type of CAR T cell therapy patients previously received may impact the efficacy of huCART19-IL18.

This study represents a significant development in the ongoing evolution of CAR T cell therapy, as it is the first time a cytokine-enhanced CAR T has been tested in patients with blood cancer. The researchers believe that incorporating cytokine secretion into CAR T cell design will have broad implications for enhancing cellular therapies, even beyond blood cancers.

The study has already led to several other clinical trials being planned, including studies for acute lymphocytic leukemia (ALL) and chronic lymphocytic leukemia (CLL). Another trial for non-Hodgkin’s lymphoma using a similar IL18-armored CAR T cell product is currently enrolling patients. On the manufacturing side, the team is partnering with a Penn spinout company to improve the process for how these CAR T cells are created and expanded in the laboratory before being reinfused into the patient.

Overall, this study has shown promise in treating lymphoma patients who have resisted multiple rounds of other cancer treatments, and further research is needed to fully understand its potential.

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Biochemistry

A Breakthrough in Brain Research: The Iontronic Pipette Revolutionizes Neurological Studies

Researchers have developed a new type of pipette that can deliver ions to individual neurons without affecting the sensitive extracellular milieu. Controlling the concentration of different ions can provide important insights into how individual brain cells are affected, and how cells work together. The pipette could also be used for treatments.

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The development of an iontronic pipette at Linköping University has opened up new avenues for neurological research. This innovative tool allows researchers to deliver ions directly to individual neurons without affecting the surrounding extracellular milieu. By controlling the concentration of various ions, scientists can gain valuable insights into how brain cells respond to different stimuli and interact with each other.

The human brain consists of approximately 85-100 billion neurons, supported by a similar number of glial cells that provide essential functions such as nutrition, oxygenation, and healing. The extracellular milieu, a fluid-filled space between the cells, plays a crucial role in maintaining cell function. Changes in ion concentration within this environment can activate or inhibit neuronal activity, making it essential to study how local changes affect individual brain cells.

Previous attempts to manipulate the extracellular environment involved pumping liquid into the area, disrupting the delicate biochemical balance and making it difficult to determine whether the substances themselves or the changed pressure were responsible for the observed effects. To overcome this challenge, researchers at the Laboratory of Organic Electronics developed an iontronic micropipette measuring only 2 micrometers in diameter.

This tiny pipette can deliver ions such as potassium and sodium directly into the extracellular milieu, allowing scientists to study how individual neurons respond to these changes. Glial cell activity is also monitored, providing a more comprehensive understanding of brain function.

Theresia Arbring Sjöström, an assistant professor at LOE, highlighted that glial cells are critical components of the brain’s chemical environment and can be precisely activated using this technology. In experiments conducted on mouse hippocampus tissue slices, it was observed that neurons responded dynamically to changes in ion concentration only after glial cell activity had saturated.

This research has significant implications for neurological disease treatment. The iontronic pipette could potentially be used to develop extremely precise treatments for conditions such as epilepsy, where brain function can be disrupted by localized imbalances in ion concentrations.

Researchers are now continuing their studies on chemical signaling in healthy and diseased brain tissue using the iontronic pipette. They also aim to adapt this technology to deliver medical drugs directly to affected areas of the brain, paving the way for more targeted treatments for neurological disorders.

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Brain Tumor

Hair-like Electrodes Revolutionize Brain Activity Monitoring

Researchers have created a hairlike device for long-term, non-invasive monitoring of the brain’s electrical activity. The lightweight and flexible electrode attaches directly to the scalp and delivers stable, high-quality electroencephalography (EEG) recordings.

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In the realm of electroencephalography (EEG) monitoring, researchers at Penn State have made a groundbreaking discovery – one that could revolutionize the way we monitor brain activity. Gone are the days of cumbersome metal electrodes; instead, a team of scientists has created hair-like devices for non-invasive, long-term monitoring.

The innovative electrode is designed to mimic human hair and can be worn without drawing attention. This lightweight and flexible device captures stable, high-quality recordings of the brain’s signals for over 24 hours of continuous wear. The traditional metal electrodes used in EEG monitoring are rigid and can shift when someone moves their head, compromising data uniformity.

The new electrode uses a 3D-printed bioadhesive ink that allows it to stick directly onto the scalp without any gloopy gels or skin preparation. This minimizes the gap between the electrode and skin, improving signal quality. The device is also stretchable, ensuring it stays put even when combing hair or wearing a baseball cap.

The researchers found that the new device performed comparably to gold electrodes, the current standard for EEG monitoring. However, the hair-like electrode maintained better contact between the electrode and skin and performed reliably for extended periods without any degradation in signal quality.

According to Tao Zhou, Wormley Family Early Career Professor of Engineering Science and Mechanics, this technology holds promise for use in consumer health and wellness products, as well as clinical healthcare applications.

The conventional EEG monitoring process can be a cumbersome affair, requiring the application of gels to maintain good surface-to-surface contact between the electrodes and skin. This process is imprecise and can result in different amounts of gel used on the electrodes, affecting brain signal quality.

Zhou explained that this new device will change the impedance – or interface – between the electrodes and scalp, ensuring more consistent and reliable monitoring of EEG signals. The researchers also hope to make the system wireless in the future, allowing people to move around freely during recording sessions.

The team’s findings were published in a study in npc biomedical innovations, with funding from various institutions, including the National Institutes of Health and Oak Ridge Associated Universities.

In conclusion, the development of hair-like electrodes for brain activity monitoring is a significant breakthrough that could revolutionize the field. With its potential for non-invasive, long-term monitoring, this technology has far-reaching implications for healthcare and consumer products alike.

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