Glioblastoma is the most common type of brain cancer, and one of the most violent and deadly cancers in humans; the average life expectancy of glioblastoma patients is 12 to 15 months from the moment of detection. Usually, the scientific monitoring of the development of the cancerous tumor in animal models is carried out without an active immune system, in order to enable the absorption and growth of cancer cells in the body. The disadvantage of this commonly-used model lies in the fact that the immune system either does not exist or does not function properly, which prevents researchers from monitoring the interaction between it and the tumor cells.

A new Tel Aviv University study examined for the first time the development of a glioblastoma cancerous tumor in animal models with a normal immune system in order to best simulate the development of the tumor in humans. The findings showed that there are immune system cells that, despite the fact that their primary function is to attack and kill the cancer cells, actually act as “double agents” that increase and intensify the aggressiveness and threat of the tumor.

The study was led by Dr. Dinorah Friedmann-Morvinski of The George S. Wise Faculty of Life Sciences and Sagol School of Neuroscience, and her PhD student Prerna Magod. Also participating in the study were Dr. Liat Rousso-Noori and Ignacio Mastandrea, also from the Faculty of Life Sciences, as well as researchers from the Sackler Faculty of Medicine and the Weizmann Institute of Science. The study was published in the prestigious journal Cell Reports.

Switching Sides

In the study, the researchers found that cells called neutrophils play a critical role in interacting with the cancerous growth. Neutrophils are immune system cells that originate in the bone marrow, and whose purpose is to “swallow” or kill bacteria and fungi and fight the infections caused by them. “Neutrophils are the front-line soldiers of the immune system,” explains Dr. Friedmann-Morvinski. “When a tumor begins to develop, the neutrophils are among the first to mobilize and attack it in order to eliminate it.”

The researchers also found that the neutrophils remain near the tumor throughout its development, and are continuously and consistently recruited from the bone marrow. The surprising thing that was discovered during this study is that the neutrophils “change sides:” Whereas at first, with the onset of the initial tumor, the neutrophils fight it, over time the neutrophils recruited to the cancerous area begin to support its development.

Dr. Friedmann-Morvinski: “We learned that the neutrophils actually change their role. They are mobilized by the tumor itself, and from being anti-cancerous, become pro-cancerous; as a result, they aggravate the damage that the tumor itself creates.”

Moreover, the researchers found that the process by which the neutrophils change their properties can take place remotely, even before they progress towards the tumor itself.

“The study showed that the change in the properties of neutrophils takes place in the bone marrow itself – where there is no tumor at all: the cancerous tumor is located only in the brain, and from there it succeeds in changing the properties of the cells it recruits,” adds Dr. Friedmann-Morvinski.

Seeking to Boost Effectiveness of Immunotherapy

“The new findings of this study may also shed light on immunotherapeutic therapies, which have been gaining a lot of momentum in recent years. In one type of immunotherapy treatment, T cells [important white blood cells of the immune system] are removed from the patient’s body, processed, and returned to the body with increased healing abilities. One of the major problems today is that even these cells, that have been sent in order to heal, are suppressed and their actions stifled. If we know how to change the interaction between neutrophils and T cells so that they are not suppressed, this will have implications for the effectiveness of immunotherapy.”

These revelations may be the first step towards deciphering the mechanism of interaction between the immune system and cancerous tumors.

Tel Aviv University researchers have found that our body’s natural defenses can help destroy malignant tumors. The team found that white blood cells called ‘eosinophils’ fight cancer in two ways: they can destroy the cancer cells themselves, and also recruit the immune system’s cancer-fighting T-cells – another type of white blood cells key to protecting the body against infection. These findings may contribute to the development of new immunotherapies.

Fighting Cancer from Within

The discovery comes as the rising number of cancer cases every year has contributed to a boom in immunotherapy, a treatment that activates the body’s immune system to fight disease. Compared to traditional techniques like chemotherapy, immunotherapy generally leads to longer protection from cancer and fewer side effects.

“Enhancing the number and power of T-cells is one of the main targets of immunotherapy treatments administered to cancer patients today,” said lead researcher, Prof. Ariel Munitz of TAU’s Department of Microbiology and Clinical Immunology at the Sackler Faculty of Medicine. “We discovered a new interaction that summons large quantities of T-cells to cancer tissues, and our findings may have therapeutic implications. Ultimately, our study may serve as a basis for the development of improved immunotherapeutic medications that employ eosinophils to fight cancer.”

Repurposing Cells’ “Destructive” Qualities

Eosinophils produce powerful destructive proteins originally intended for fighting parasites. However, in the modern Western world, where high levels of hygiene have significantly reduced the risk of many parasites, eosinophils often have a negative impact on humans, inducing phenomena like allergies and asthma.

Considering the destructive power of eosinophils, the researchers decided to test the potential benefits of these white blood cells if turned against cancer cells.

For two main reasons, they decided to focus their study on lung metastases, or cancer that started in another part of the body and spread to the lungs: “First, metastases, and not the primary tumors, are often the main problem in treating cancer. The lungs are a major target for the metastasis of many types of cancer,” said Prof. Munitz. “Second, in a preliminary study we demonstrated that eosinophils gather in tumors developing in mucous tissues like the lungs, and therefore assumed that they would be found in lung metastases as well.”

Summoning Reinforcement

The researchers examined tissue samples taken from breast cancer patients. They found that the eosinophils reach the lungs and penetrate the cancer tissues, where they often release their destructive proteins and summon T-cells for reinforcement. Ultimately, T-cells gather in the affected lungs, slowing the growth of tumors.

Additionally, the researchers found that in the absence of eosinophils, the lung tumors were much larger than those exposed to the white blood cells. These findings led to the conclusion that eosinophils fight cancer effectively.

Along with Prof. Munitz, the study was led by TAU PhD student Sharon Grisaru. The findings were published in the journal Cancer Research, published by the American Association for Cancer Research. The initiative was funded by ICRF (Israel Cancer Research Fund), the Israel Cancer Association, ISF (the Israel Science Foundation) BSF (U.S.-Israel Binational Science Foundation) and GSK.  

Featured image: Illustration: Eosinophil, a white blood cell in 3D

Approximately 50 million people worldwide live with Alzheimer’s or other related forms of dementia. Alzheimer’s disease leads to memory loss and impairment in cognitive function, and is the most common cause of dementia among older adults. While certain treatments can help reduce symptoms and sometimes reduce disease progression, there is currently no way to prevent or cure Alzheimer’s.

Amid that backdrop, researchers from Tel Aviv University have developed a process for reversing the precursors of the disease, providing a promising foundation for new preventative therapies. This marks the first time that a non-drug therapy has proven effective in preventing the core biological processes that lead to the development of Alzheimer’s, providing hope that we will now be able to fight one of the greatest challenges to the Western world.

Targeting the Root of Alzheimer’s

Using hyperbaric oxygen therapy (HBOT), in which subjects breathe 100% oxygen in a special chamber of high atmospheric pressure, the researchers were able to reverse brain damages associated with the biological hallmarks of Alzheimer’s.

 “By treating the root problem that causes cognitive deterioration with age, we are in fact mapping out the way to prevention,” says co-lead researcher Prof. Shai Efrati.

Often used to treat carbon monoxide poisoning and infections that starve tissues of oxygen, hyperbaric therapy, when applied in a specific way, has previously been found capable of repairing damaged brain tissue and renewing growth of blood vessels and nerve cells in the brain. Therefore, the researchers tested its potential for Alzheimer’s.

“After a series of hyperbaric treatments, elderly patients who were already suffering from memory loss showed an improvement of blood flow to the brain as well as a real improvement in cognitive performance,” said co-lead investigator Prof. Uri Ashery.

The new approach devised by the researchers unequivocally improved characteristics commonly associated with Alzheimer’s disease. Specifically, the hyperbaric treatment resulted in:

• Improved memory in 16.5% of patients on average
• Increased blood flow in 16%-23% of cases
• Improved attention and concentration in 6% of patients
• Improved information processing speed in 10.3% of all cases

A Future Without Alzheimer’s?

 “Our findings provide hope that we will now be able to fight one of the greatest challenges to the Western world. According to our findings, hyperbaric therapy given at a young age is likely to prevent this severe disease entirely,” explains TAU team member Dr. Ronit Shapira.

The approach was first tested in laboratory settings followed by testing in patients over the age of 65 in stages of deteriorating mental function that often precede Alzheimer’s and dementia. The therapy included a series of 60 treatments in hyperbaric chambers over a period of 90 days.

The study is part of a comprehensive research program focused on reversing processes of aging and its accompanying ailments. The researchers note that the findings are an encouraging step toward new approaches to preventing Alzheimer’s by addressing not only the symptoms or targeting biomarkers, but the core pathology and biology responsible for the disease’s development.

The Tel Aviv University team that led the study included Prof. Shai Efrati of the Sackler Faculty of Medicine and the Sagol School of Neuroscience, Prof. Uri Ashery and  Dr. Pablo Blinder of the The George S. Wise Faculty of Life Sciences and the Sagol School of Neuroscience, and Dr. Ronit Shapira and Dr. Amir Hadanny. They are all affiliated with the Shamir Medical Center. The findings were published in the journal Aging.

Featured image: Alzheimer’s Disease on MRI

Warnings against the dangers of smoking can be read on every cigarette box and in every advertisement for smoking brands. Those who smoke endanger themselves and also those around them, who inevitably become passive smokers. This way, parents who smoke harm the health of their own children. A first-of-its-kind study in Israel by researchers from the Sackler Medical School of Tel Aviv University uncovers alarming data about secondhand smoking by children of smokers: According to the study, nicotine residues were found in the hair samples of 7 out of 10 children who participated. The research team found that parental behavior may be changed through regular monitoring of children’s exposure.

Nicotine Residue in Children’s Hair

The study was conducted under the leadership of a team of experts from the Tel Aviv University School of Medicine headed by Prof. Leah (Laura) Rosen of the School of Public Health together with researchers Dr. Vicki Myers, Prof. Nurit Guttman, Ms. Nili Brown, Prof. Mati Berkovitch, and Dr. Michal Bitan. Prof. David Zucker of the Hebrew University of Jerusalem and Dr. Anna Rule of Johns Hopkins University in the US also participated in the study. The study was published in the prestigious journal, Nicotine & Tobacco Research.

In the study, the researchers sought to examine whether raising awareness of children’s exposure by providing objective feedback might change the parents’ behavior and child exposure. 140 Israeli families participated in the study, parents of children up to age 8, at least one parent being a smoker. The smoking average per household was 15 cigarettes per day, where one third of the respondents reported that they smoke inside the home, and one third said that they smoke on the terrace but not inside the home.

First, researchers tested children’s level of exposure via a biomarker, nicotine in hair, which indicates cumulative exposure to tobacco smoke. The researchers took hair samples from the children and tested the nicotine levels in each sample (it is important to note that the test was for nicotine that became an integral part of the strand of hair and not just outside precipitate.) The findings were very concerning: Nicotine residue was found in the hair of 70% of the children tested. Only 29.7% of the children tested did not show nicotine residue in their hair samples. 

The researchers divided the families into two groups: one group underwent comprehensive instruction about the effects and dangers of exposure to smoking, including feedback and information about the test results. The group was also given tools to protect their children from exposure to cigarette smoke and a recommendation to keep their home and car smoke-free. The second group received feedback about nicotine levels in the children’s hair after six months, at the end of the study.

Limiting Children’s Exposure

Six months after the start of the study, the researchers conducted additional nicotine tests on the children’s hair, and one could already see a significant improvement in the data: Among the group that received comprehensive training, the percentage of children whose hair samples contained nicotine decreased from 66% to 53%, whereas in the second group (which did not receive training at the start of the study), the percentage of children whose hair samples contained nicotine decreased from 74% to 49%. Thus, just testing the children, without even informing families of the results, was enough to seemingly change parents’ behaviors.

The researchers theorize that the knowledge that the children were tested for tobacco smoke exposure, and that additional testing was planned at six months, resulted in the parents changing their behavior and reducing the children’s exposure. As a result of the study’s findings, the researchers recommend considering conducting such testing to measure exposure on a routine basis among young children in Israel.

The Right to Breathe Smoke-Free Air

Prof. Leah Rosen: “To our great dismay, according to the Ministry of Health’s data, approximately 60% of small children in Israel are exposed to secondhand smoke and its harmful effects. Based on the study’s findings, we believe that conducting nicotine testing – in the hair, urine, or using other testing methods – for every young child in Israel, may change parents’ perceptions about exposing their children to tobacco smoke. Changing this perception can also result in changing behavior, exposure levels, and even social norms regarding passive exposure to smoking – both exposure of children as well as exposure of adults.”

“We call upon smokers to avoid smoking anyplace where non-smokers and in particular, at-risk populations, including children, pregnant women, elderly, and those who are ill, could be exposed. Non-smokers must understand that there is genuine risk in exposure to tobacco smoke, and they must insist upon their right and the right of their children and family members to breathe air that is smoke-free everywhere. Of course, the government has a central role in enforcing laws pertaining to smoking in public places and continuing to enact laws to protect the individual everywhere from exposure to secondhand smoke.”