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Despite the success of immunotherapy in helping many people with cancer, the majority of patients still do not respond to these treatments. There is need for continued research.
On April 20, 2022, researchers at the Sloan Kettering Institute reported in the journal Nature that a recently discovered new immune cell “soldier” could be a good target for immunotherapy, raising hopes that it might help narrow the gap between people who respond and those who do not.
The new cells, which the scientists have dubbed killer innate-like T cells, differ in notable ways from the conventional target of many immunotherapies — the cytotoxic (aka “killer”) T cells. For one, they don’t get exhausted from extended activity like cytotoxic T cells do. And two, they can penetrate more deeply into tissues where cancer is hiding. These unique attributes make them attractive as a target for immunotherapy.
“We think these killer innate-like T cells could be targeted or genetically engineered for cancer therapy,” says Ming Li, an immunologist in SKI and the lead author of the new study. “They may be better at reaching and killing solid tumors than conventional T cells.”
Pinning Down What Makes the Cells Distinct
Dr. Li’s team first reported the existence of this unusual cell population in 2016. At that time, it was clear to his team that these cells had the power to kill cancer cells, but they knew little about where the cells come from or how they work.

Radiation therapy is a proven approach to destroying tumours. However, it is possible that it might be able to do even more in the future — namely stimulate the immune system at the same time and so fight cancer even more intensively. The foundations for this have been laid by researchers led by TU Darmstadt. They have found that x-rays trigger a calcium signalling cascade in cells of the immune system. The results have now been published in the Journal of General Physiology.
Ionising radiation is successfully used in cancer treatment to kill tumour cells. Over the past two decades, it has become clear that treatment success can be increased even further if the radiation treatment is combined with measures to stimulate the immune system. In this context, a new study being carried out with biologists from TU Darmstadt and the GSI Helmholtz Centre for Heavy Ion Research plus researchers from the clinics of the Frankfurt and Homburg universities is attracting attention. The researchers report in the Journal of General Physiology that the desired stimulating effect on the immune system is triggered directly when T-cells are also irradiated by x-rays. Dominique Tandl, researcher at the Department of Biology at TU Darmstadt, and her co-authors demonstrate in the recently published study that clinically relevant doses of x-rays in T lymphocytes trigger a signalling cascade that is typical of the immune reaction that begins with the release of the messenger substance calcium (Ca2+) from internal stores.
Activated by what is known as store operated Ca2+ entry (SOCE), the concentration of Ca2+ in the cells begins to oscillate at a critical frequency, which in turn leads to the displacement (translocation) of a transcription factor from the cytoplasm into the cell nucleus. Once there, this transcription factor initiates gene expression, and the cell begins to make molecules that are important for the immune response, such as cytokines. Since the irradiation of tumours invariably always affects the blood cells in the target tissue, medicine could utilise the stimulating effect of x-rays on T lymphocytes. The researchers hope that their studies will contribute to improving cancer treatment in the long term, as Professor Gerhard Thiel, head of the Membrane Biophysics Group at the Department of Biology at TU Darmstadt and co-author of the study, says. “It could be possible to enhance the killing effect of ionising radiation on tumour cells and at the same time to stimulate the immune system with the help of this radiation.”
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In a study published today in the journal Nature Communications, researchers at the Lewis Katz School of Medicine at Temple University defined 11 subsets of cells found in the esophagus of mice, information that could potentially help clinicians diagnose or treat certain types of cancer.
The tissue in the esophagus — known as stratified squamous epithelium — is composed of a basal layer that ultimately gives rise to several layers of differentiated cells. In this study, researchers sought to find out whether basal cells were all the same or if any differences existed in their gene expressions.
“This work lays the foundation to address questions about how these cells relate to the development of cancer,” said Kelly Whelan, PhD, senior author on the study and Assistant Professor of Cancer and Cellular Biology and Assistant Professor in the Fels Cancer Institute for Personalized Medicine at the Lewis Katz School of Medicine.
“The next question we have is if we give a mouse a carcinogen, does one particular subset expand or is another particular subset depleted? If so, we would want to know whether cell types that change in the context of cancer are functionally contributing to the cancer process and whether we can target them to help treat or prevent cancer,” she said.
To begin to address these questions, Whelan and her fellow researchers used single cell gene-expression profiling, a tool that identifies all the genes in a cell or tissue that make messenger RNA. These profiles can then be used to identify individual cell types within a complex tissue.
“Essentially, we took more than 40,000 cells from mouse esophageal epithelium and used their individual gene-expression profiles to group them based on their commonality,” she said.
When they started the study, Whelan said the researchers expected to find about three subsets of cells classified as basal, but they actually found six subsets, as well as four that were classified as differentiated. Additionally, one cell type was found to have characteristics of both basal and differentiated cells and was defined as an intermediate cell type.
“We are now working to isolate these individual cell types in order to determine what the cells do functionally in terms of esophageal biology in the normal context first and then in the context of cancer. This study is a fundamental step toward that,” said Whelan.
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When the bacterium Helicobacter pylori infects the stomach, it causes gastric inflammation and increases the risk of stomach cancer. A team of researchers from Charité — Universitätsmedizin Berlin and the Max Delbrück Center for Molecular Medicine (MDC) have been able to elucidate characteristic changes which occur inside the gastric glands during an H. pylori infection. The researchers discovered a novel mechanism which, by restricting cell division in healthy stomach tissue, protects the stomach against cancerous changes. An inflammation of the stomach, however, deactivates this mechanism, enabling cells to grow in an uncontrolled manner. The researchers’ findings, which have been published in Nature Communications, may herald a new treatment target in stomach cancer.
Affecting about half the world’s population, Helicobacter pylori is one of the most common causes of chronic bacterial infections in humans. H. pylori can lead to inflammation of the stomach (gastritis) and increase the risk of developing stomach cancer. As the protective lining inside the stomach is constantly exposed to stomach acid, it has to regenerate completely every few weeks, while maintaining both its structure and composition despite the high cellular turnover. “Until now, researchers had assumed that a Helicobacter infection causes direct damage to the gastric gland cells in the stomach lining and that gastric pathology upon infection is simply the result of this process,” explains the study’s last author, Prof. Dr. Michael Sigal. He continues: “In fact, our team has now discovered that the infection disrupts complex interactions between different cell types and signals which are responsible for tissue stability.” Prof. Sigal is Professor for Translational Gastrointestinal Oncology and leads an Independent Research Group at Charité’s Department of Hepatology and Gastroenterology and the Berlin Institute for Medical Systems Biology (BIMSB), which forms part of the MDC.
Led by Prof. Sigal and working alongside colleagues from the Max Planck Institute for Infection Biology, the team of researchers used complex mouse models to observe changes occurring inside the gastric glands. Using state-of-the art imaging and single-cell sequencing technologies, the researchers were able to visualize and isolate specific gastric gland cells, which they then examined in detail. In order to minimize the need for animal models, they also developed special organ-like tissue microstructures known as organoids. The researchers used these microscopic stomachs to recreate many of the gastric glands’ characteristics. This strategy enabled them to study the effects of various signals on stem cells which are found inside the gastric glands (and which are capable of differentiating into many different cell types).
“We discovered that ‘stromal cells’ — a type of cell surrounding the gastric glands — are not only responsible for mechanical stability of the glands, as previously thought. Instead, they produce various signaling molecules which significantly influence the behavior of the gland cells,” explains Prof. Sigal. These substances include ‘bone morphogenetic proteins’ (BMPs), which play an important role in tissue development. The researchers were able to show that stromal cells surrounding the gland base continually inhibit the BMP signaling pathway, thereby stimulating the proliferation of nearby stem cells. In contrast, stromal cells at the gland surface were found to activate the signaling pathway, thereby suppressing cell proliferation. Together, this forms a signaling gradient that guides stem cell turnover and differentiation, and serves as the basis for the gland’s structural stability. Helicobacter infection causes the release of pro-inflammatory substances such as interferon-gamma (IFN-γ). This inflammatory cytokine interferes with the BMP signaling axis, resulting in less BMP signaling activity and stimulating gland stem cell proliferation. This results in hyperplasia, a precancerous lesion characterized by tissue enlargement.
“Our findings show that an infection-driven inflammatory response has far more pronounced effects than previously thought. In addition to their well-characterized antimicrobial effects, pro-inflammatory substances such as IFN-γ affect both cell proliferation and tissue stem cell behavior and therefore have a direct impact on tissue homeostasis. In the case of tissue damage, increased cell proliferation can be useful, as it promotes rapid healing. In the case of chronic inflammation associated with a Helicobacter infection, however, it could facilitate the development of precancerous lesions,” summarizes Prof. Sigal. The signaling pathways governing interactions between the immune system and stem cells in the stomach could also prove significant in other organs. As such, they represent a new treatment target — both in cancer prevention and regenerative medicine.
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Everyone wants to stay fit and healthy as they grow old. But as we age, our body degrades, our muscles shrink and strength declines. Some older people suffer from excessive muscle loss, a condition known as sarcopenia. University of Basel researchers show that a combination therapy could delay the onset of sarcopenia.
We now live longer than at any point in human history, but to enjoy those extra years, we need to remain healthy, mobile and independent. With age, however, our muscles inevitably lose mass and strength. This age-related muscle loss puts an end to an autonomous lifestyle for many elderly people, who must then rely on family or the healthcare system for daily support.
Slowing age-related muscle loss
“Age-related muscle decline already occurs in our thirties but begins to accelerate at around 60. By age 80, we have lost about a third of our muscle mass,” says Dr. Daniel Ham, one of the lead authors of the study now published in “Nature Communications”. “Although this aging process cannot be stopped, it is possible to slow it down or counteract it, for example through exercise.”
Researchers led by Professor Markus Rüegg at the Biozentrum of the University of Basel have demonstrated in mice that both calorie restriction and the drug rapamycin have a positive effect on aging skeletal muscle. “If we can understand what happens in the muscle as we age, perhaps we can design treatments to counteract muscle aging and prevent sarcopenia.”
“Both calorie restriction and rapamycin have been proposed as anti-aging interventions, but we didn’t expect the two treatments to provide additive benefits,” explains Dr. Nitish Mittal, another lead author of the study. Previously, it was thought that moderate fasting and rapamycin represent different means of achieving the same goal, namely suppression of the protein complex mTORC1, which accelerates aging when overactive.
Beneficial effects enhanced with combined treatment
“Contrary to our expectations, the treatments do not redundantly converge at mTORC1,” emphasizes Ham. “While we could understand that calorie restriction would have beneficial effects beyond mTORC1 suppression, it was incredibly surprising to us that rapamycin, an mTORC1 inhibitor, further slowed muscle aging in calorie restricted mice, where mTORC1-activating nutrients are available for just a few hours each day.” In calorie-restricted mice treated with rapamycin, the beneficial effects were therefore additive, with mice displaying significantly better muscle function than mice receiving either treatment alone. “Compared to their peers, treated mice are more active and physically capable because their muscles remain healthy,” says Ham.
Healthy muscles for longer independence
“The health of our muscle really is wealth. Beyond physical function, muscles are essential for whole-body metabolism and the proper functioning of many organs,” says Mittal. The positive impact of calorie-restricted diets and rapamycin on muscle aging leads to the intriguing question of whether elderly people suffering from sarcopenia can profit from a combined therapy consisting of an mTORC1 inhibitor, a calorie restriction-mimicking drug and perhaps exercise.
“Strong and healthy muscles provide many benefits for elderly people, in fact for all of us,” says Ham. “We can live an active and independent life for longer, and enjoy activities such as hiking, traveling or taking care of the grandkids.” This plays a major role in life quality and satisfaction in old age and also relieves the health care burden.
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A new study of genetic data published today (Wednesday) of more than 400,000 UK adults has revealed a clear link between walking pace and a genetic marker of biological age.
Confirming a causal link between walking pace and leucocyte telomere length (LTL) — an indicator of biological age — the Leicester-based team of researchers estimate that a lifetime of brisk walking could lead to the equivalent of 16 years younger biological age by midlife.
Researchers from the University of Leicester at the National Institute for Health Research (NIHR) Leicester Biomedical Research Centre studied genetic data from 405,981 middle-aged UK Biobank participants and found that a faster walking pace, independent of the amount of physical activity, was associated with longer telomere.
Telomeres are the ‘caps’ at the end of each chromosome, and hold repetitive sequences of non-coding DNA that protect the chromosome from damage, similar to the way the cap at the end of a shoelace stops it from unravelling.
Each time a cell divides, these telomeres become shorter — until a point where they become so short that the cell can no longer divide, known as ‘replicative senescence’. Therefore, scientists consider LTL a strong marker for ‘biological age’, independent from when an individual was born.
Although the relationship between telomere length and disease is not fully understood, the build-up of these senescent cells is believed to contribute to a range of symptoms we associate with aging, such as frailty and age-related diseases.

New research into human speed from a team at SMU (Southern Methodist University,) and West Chester University suggests that athletes who performed short sprints with their arms closed across their chests were nearly as fast as when they sprinted with their normal arm swing.
The findings, published in the journal Gait & Posture, offer additional fundamental insights regarding limb synchronization during sprint performance.
“Our findings suggest the classic view that arm swing directly drives leg motion to affect performance is not well-supported,” said Peter Weyand, an expert in human speed who leads SMU’s Locomotor Performance Lab.
The coauthors of the research are lead author Lance C. Brooks, a doctoral student studying with Weyand in the Department of Applied Physiology & Wellness; Weyand, who is Glenn Simmons Endowed Professor of Applied Physiology and Biomechanics in the Department of Applied Physiology & Wellness in SMU’s Annette Caldwell Simmons School of Education & Human Development; and Kenneth P. Clark, an associate professor in the Department of Kinesiology at West Chester University. Brooks previously studied under Clark at West Chester University as he completed his master’s degree in exercise science and biomechanics.
The study examined the velocity of participants first sprinting 30 meters with regular arm motion, then again with restricted arm motion. When study participants sprinted with restricted arm motion, their 30-meter sprint time slowed down by only 0.08 seconds on average, a 1.6 percent difference from when the participants sprinted while moving their arms.
“We were surprised by the small magnitude of difference between the two experimental conditions. It is generally believed that the arms substantially influence the movement of the legs, and therefore running speed, which clearly is not the case,” Brooks said.
“When the athletes sprinted with restricted arm swing, the torso rotated back and forth appreciably more than normal to counterbalance the swinging legs,” Brooks added. “We believe that this extra torso rotation effectively compensated for arm swing to help maintain the body’s forward-facing orientation and the overall mechanics needed for speed.”
The study’s results strongly suggest that human runners use arm motion to prevent the body from rotating away from its forward-facing orientation.
“The compensatory torso twisting movements we observed during arm motion restriction indicate that runners swing their arms as the simplest and most natural strategy to prevent undesirable bodily rotations,” Clark said.
Do the team’s findings mean we will see less arm-swinging among sprinters in competitive sprinting? Probably not, as the difference in timed results is often razor-thin in timed competitions. The researchers point to the results of the 2020 Olympics Men’s 100-meter final, where the difference between the Gold and Bronze medal was only 0.09 seconds.
But the study’s findings are still an important step toward better understanding the influence of arm rotation on sprint performance.
“Virtually all runners choose to swing their arms to maintain a forward-facing position,” Weyand said. “The classic studies on the ‘why’ of arm motion during human locomotion are 40 or more years old and focused primarily on walking and jogging. So, performance effects were largely unknown,” he said.
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Plastics surround us, whether it’s the grocery bags we use at the supermarket or household items such as shampoo and detergent bottles. Plastics don’t exist only as large objects, but also as microscopic particles that are released from these larger products. These microscopic plastics can end up in the environment, and they can be ingested into our bodies.
Now, researchers at the National Institute of Standards and Technology (NIST) have analyzed a couple of widely used consumer products to better understand these microscopic plastics. They found that when the plastic products are exposed to hot water, they release trillions of nanoparticles per liter into the water.
The NIST researchers published their findings in the scientific journal Environmental Science and Technology.
“The main takeaway here is that there are plastic particles wherever we look. There are a lot of them. Trillions per liter. We don’t know if those have bad health effects on people or animals. We just have a high confidence that they’re there,” said NIST chemist Christopher Zangmeister.
There are many different types of plastic materials, but they are all made up of polymers, natural or human-made substances composed of large molecules linked together. Scientists have found microscopic particles from these larger plastics in the oceans and many other environments. Researchers categorize them into two groups: micro- and nanoplastics.
Microplastics are generally considered smaller than 5 millimeters in length and could be seen by the naked eye, while nanoplastics are smaller than one millionth of a meter (one micrometer) and most can’t even be seen with a standard microscope. Recent studies have shown some consumer products that hold liquids or interact with them, such as polypropylene (PP) baby bottles and nylon plastic tea bags, release these plastic particles into the surrounding water.

Cancer researchers at the Case Western Reserve University School of Medicine say they have successfully suppressed the growth of some solid tumors in research models by manipulating immune cells known as a macrophages.
The researchers say this discovery is significant as many solid tumor cancers like lung cancer are difficult to treat. According to the National Cancer Institute, breast, lung, prostate and colorectal cancers — which are all solid tumor cancers-account for almost half of all new cancer cases in the United States.
In this new research, the scientists discovered that altering the macrophage metabolism — and in doing so influence their relationship with T cells — suppressed the tumor’s growth. The result was a significant reduction in overall tumor size in some mouse models.
“The race to find a cure for cancer never stops,” said Stanley Huang, an assistant professor of immunology in the Department of Pathology at the School of Medicine, who led the research. “Our research creates a pathway to a [potential] new form of cancer treatment for those with solid tumor cancers.”
The study appeared recently in the journal, Nature Immunology.
T cells and macrophages
Generally, the body’s immune response to disease involves mobilizing white blood cells that attack invaders like germs and bacteria.

Since its inception, the Internet has fundamentally changed all parts of human society for both good and ill, and medical research is no exception. The fast pace of change enabled by digital technologies means that ethical guidelines may not address all the issues that arise in modern research. To help solve this problem, researchers from Osaka University performed an ethical analysis based on the eight ethical principles for clinical research and they proposed an ethical framework and practical guidance for communicating with research participants through the Internet.
The ability to recruit study participants regardless of geography is a major advantage of electronic communications, such as for studies of rare diseases, where it is often difficult to find enough participants in a defined geographic area to ensure scientific validity. However, the ease and scale of electronic communications has also led to serious problems such as violations of privacy, duplicate registrations, and misinformation that existing ethical guidelines didn’t anticipate.
“Currently, there are no comprehensive rules or guidelines for the various electronic methods used to communicate with research participants,” says Atsushi Kogetsu, lead author of the study, “and that includes methods for collecting electronic informed consent and online recruitment.” Hence, the authors performed an ethical analysis to determine what the issues are and how they relate to each other.
The analysis is based on the Emanuel framework, which consists of eight ethical principles for clinical research: collaborative partnership, social value, scientific validity, fair participant selection, favorable risk-benefit ratio, independent review, informed consent, and respect for participants. For instance, the researchers found that although there are many advantages to online communications, it is important to consider how patient access to the Internet varies according to circumstances and culture, which could affect participant recruitment, leading to selection bias.
“We also need to be careful how we present information to study participants,” says Kazuto Kato, co-author of the study. “It’s important to remember that the lack of nonverbal information when using some online tools can lead to miscommunication. We need to make sure that information is complete and accurate but not overwhelming.”
The proposed framework covers both the specific processes involved in medical research (from research design to the dissemination of results) and three overarching perspectives (access to research, community involvement, and independent review). It provides the practical steps independent reviewers, funding agencies, researchers, and patient partners can use to ensure all ethical guidelines are followed. The researchers believe the results of this study and its framework will improve future practice in medical research using the Internet.
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