Facts and common misconceptions about some of America’s most widely used drugs.Antidepressants are among the most prescribed medications in the United States. This is, in part, because the number of people diagnosed with depression and anxiety has been on the rise, and prescriptions jumped sharply among some age groups during the pandemic.Despite the prevalence of these medications, some patients have “significant misconceptions” about how the drugs work, said Dr. Andrew J. Gerber, a psychiatrist and the president and medical director of Silver Hill Hospital in New Canaan, Conn.About 80 percent of antidepressants are prescribed by primary care doctors who have not had extensive training in managing mental illness.Dr. Paul Nestadt, an associate professor of psychiatry at the Johns Hopkins School of Medicine, said patients tell him, “‘You know, Doc, I’ve tried everything.’” But often, he said, “they never got to a good dose, or they were only on it for a week or two.”Here are some answers to frequently asked questions about antidepressants.How do antidepressants work?There are many types of antidepressants, and they all work a bit differently.In general, they initiate a change in the way brain cells — and different regions of the brain — communicate with one another, said Dr. Gerard Sanacora, a professor of psychiatry at the Yale School of Medicine.We are having trouble retrieving the article content.Please enable JavaScript in your browser settings.Thank you for your patience while we verify access. If you are in Reader mode please exit and log into your Times account, or subscribe for all of The Times.Thank you for your patience while we verify access.Already a subscriber? Log in.Want all of The Times? Subscribe.

Published1 hour agoShareclose panelShare pageCopy linkAbout sharingImage source, Getty ImagesBy Marie-Louise Connolly & Aileen MoynaghBBC News NI health correspondentMore than 3,000 women who are impacted by the southern health trust’s cervical smear review and have had a recent smear test, are to have their previous slides re-checked. According to the trust, this move is not out of concern but to provide extra assurance to a group of affected women.Letters were sent to homes this week.The trust said these women have had a recent smear test as part of the cervical smear screening programme and received the result.It added it recognised the anxiety the review had caused and as a result of feedback from women affected it had agreed to their request to review old slides as part of the process.In letters, seen by BBC News NI, women have been advised of this decision.The women had previously been told this would not happen as they had attended for a routine smear and their latest result would provide the most accurate assessment of their current risk of cervical abnormalities which may develop into cancer. ‘Provide maximum reassurance’Dr Stephen Austin, Southern Trust medical director, said the additional work would likely extend the overall slide review process “by only a matter of weeks” because of support from other trust laboratories.It is expected that work on the additional phase will begin after the main review has been completed and will be finished by the end of the summer.In 2023, BBC News NI revealed about 17,500 women in the area had received letters informing them their smear tests would be rechecked.According to the trust “progress is being made” with 61% (about 10,700) of cases reviewed.While a “small number” of cases had identified “minor abnormalities” and required further testing, the trust said this was to be expected. To date no cases of cancer have been identified but trust officials warn the review is not complete. The Southern Trust and Public Health Agency (PHA) urged women to continue to come forward for their smear tests when invited.Primary HPV screeningIn December 2023, Northern Ireland introduced primary HPV cervical screening.It checks for an infection called human papillomavirus (HPV) – the cause of most cervical cancers.High-risk HPV can cause cervical cells to become abnormal and potentially develop into cancer over time.Virtually all cases of cervical cancer are linked to high-risk HPV.This newer HPV test is regarded as a better indicator than cytology of identifying who is a higher risk of developing cervical cancer.17,500 cervical smear tests to be re-checkedThird of smear tests checked under review’I have right to know about my smear test review’HPV is a common virus, and, in most cases, it will be cleared by the body’s immune system and have no adverse health impact.It is only when the virus persists, that it can cause cell changes in the cervix which, with time, can develop into cancer.The trust and PHA say it is important to emphasise again that cervical screening is not a diagnostic test.It is for people without symptoms and aims to detect early changes which could go on to develop into cervical cancer if left untreated.Anyone with symptoms should always seek advice from their GP.More on this story17,500 cervical smear tests to be re-checkedPublished9 October 2023’I have right to know about my smear test review’Published25 JanuaryThird of smear tests checked under reviewPublished5 March

Published2 hours agoShareclose panelShare pageCopy linkAbout sharingImage source, Getty ImagesBy Philippa Roxby and Elena BaileyHealth reportersA third of 11-year-olds and more than half of 13-year-olds in England have drunk alcohol – putting it top out of 44 countries examined in a report by global health experts.Girls were found to be more likely than boys to be drinking and getting drunk aged 15 in England, Wales and Scotland. The World Health Organization (WHO) report said alcohol, which can damage children’s brains, has been normalised.It called on countries to introduce more measures to protect children.The report looked at data from about 4,500 school-age children from each country in Europe, central Asia and Canada in 2021-22 on cigarette smoking, vaping, alcohol and cannabis habits among adolescents. The UK has always had relatively high alcohol use among young people but it has been declining for some time.Study coordinator Dr Jo Inchley, from Glasgow University, said signs that more children were starting to drink at a young age was “concerning”.”Trying substances is part of growing up and experimenting but alcohol has long-term effects on health,” she said.Dr Inchley said being exposed to more alcohol at home, changing attitudes of parents and the rebound effects after Covid lockdown could all be factors in the trend.Research shows the earlier children start drinking, the more serious a problem it can become when they are older.At age 13, the report found 12% of girls and 9% of boys in England had been drunk at least twice in their lives.At 15, that had risen to a third of girls and a quarter of boys. More than a half of girls said they had drunk alcohol in the past 30 days.’I wanted to drink vodka at school’Image source, Harriet StrangeHarriet Strange, 30, from Kent started drinking alcohol when she was 14. “My dad was an alcoholic so I think there’s a chance that I may have done it because it was learned behaviour from him,” she said.”Once I started drinking it was a spiral of self-destruction.”My friends were always older than me so I would get them to buy alcohol for me or I would take it from my house.”Harriet would go to house parties when she was 14 or 15 and “nobody would bat an eyelid, it was just normal”.She said she knew from an early age that her relationship with alcohol wasn’t like other people’s.”It got to the point where I wanted to drink vodka at school,” she said.”My father’s death when I was 16 was really the catalyst of absolute self-destruct.”She has been sober for three-and-a-half years now and credits becoming pregnant with her daughter for saving her life.”I know what it’s like being a child of an alcoholic and I didn’t want to give that to her.”Harriet is now a recovery coach and volunteer for Nacoa, an organisation which provides support for those affected by a parent’s drinking.Helena Conibear, from Talk About Trust, which educates children in schools about alcohol and other substances, said most children have their first drink in the family home.”If teens think parents don’t mind, they will drink outside the home,” she said.Official health advice is that children and young people should not drink alcohol before the age of 18 and, if they do, not until at least 15. This is to protect their brains and their bodies, which are too young to cope with it.Vaping rates risingThe report also looked at other substances used by adolescents.On cannabis use, the report found more boys in Scotland had used the drug (23%) compared to all other countries surveyed. Cannabis use has dropped and stabilised in recent years but some vulnerable children are still continuing to use it, said Dr Inchley.No data on cannabis was provided for England.Smoking among children is much less common than it used to be – one in five 15-year-old girls said they had ever smoked a cigarette – but smoking rates are still higher among girls than boys in England and Wales. The report confirmed that vaping rates have overtaken cigarette smoking in most countries, with nearly one in 10 11-year-olds saying they’ve used a vape at least once, rising to 26% of boys and 40% of girls by age 15.Vaping rates in the UK are above average, compared to other countries. Even though vaping is thought to be much less dangerous than smoking, the risks of children breathing chemicals into their lungs are not yet fully understood. The UK government has already introduced measures to clamp down on the promotion and illegal sale of vapes to under 18s. Dr Hans Kluge, WHO regional director for Europe, said harmful substance use among children in many countries was “widespread” and “a serious public health threat”.He said children were constantly exposed to harmful products online and that video games were helping to make drinking, smoking and vaping seem acceptable and normal.The report urged countries to introduce measures to protect younger generations, such as limiting the availability of nicotine and tobacco products, alcohol and a ban on advertising and promotion of any substances on mainstream and social media.Related Internet LinksCoping With Life – Mental Health Advice – YoungMinds – YoungMindsDrugs and Alcohol – Support For Young People – YoungMindsHow to talk to your child about alcohol – DrinkawareKnow the risks of underage drinking – DrinkawareCannabis – Weed – Effects of Cannabis – FRANKNacoa – Helping everyone affected by their parent’s drinkingWHO report on adolescent substance use in Europe, central Asia and CanadaThe BBC is not responsible for the content of external sites.

Weill Cornell Medicine investigators have uncovered a way to unleash in blood vessels the protective effects of a type of fat-related molecule known as a sphingolipid, suggesting a promising new strategy for the treatment of coronary artery disease.
In the study, published March 8 in Circulation Research, the researchers showed that boosting levels of a sphingolipid called S1P in artery-lining endothelial cells slows the development and progression of coronary artery disease in an animal model. The lead author was Dr. Onorina Laura Manzo, a postdoctoral researcher in the laboratory of Dr. Annarita Di Lorenzo, an associate professor of pathology and laboratory medicine at Weill Cornell Medicine.
Sphingolipids are named for the enigmatic sphinx of ancient mythology because their functions in biology traditionally have been somewhat mysterious. In recent years, there has been increasing evidence of their relevance in coronary artery disease; bloodstream levels of S1P, for example, are lower in patients with this condition. But the precise roles of these lipids have remained unclear.
In the new study, the researchers sought a better understanding of those roles — and of sphingolipids’ potential as therapeutic targets. Despite the availability of cholesterol-lowering drugs and other interventions, coronary artery disease — the underlying cause of most heart attacks and many strokes — continues to be the world’s leading cause of mortality, affecting more than 20 million people in the United States alone.
Using a novel mouse model developed by the same group, the researchers found that blood pressure-related stress on arteries — which eventually will induce coronary artery disease — triggers an increase in S1P production in endothelial cells, as part of a protective response. This response normally is only temporary, but deleting a protein called NOGO-B, which inhibits S1P production, allows the rise in endothelial S1P production to be sustained — and made the animals much more resistant to coronary artery disease and associated mortality.
Another key finding is related to a different group of sphingolipids called ceramides. Prior studies have linked coronary artery disease to high bloodstream levels of some ceramides, and their causative role in the disease has been widely assumed. In their model, however, the researchers observed that while ceramide levels were high in the bloodstream, levels in artery-lining endothelial cells remained about the same regardless of coronary artery disease status. This suggests that the current view of ceramides’ role in the disease should be revised.
All in all, the findings lay the foundation for the development of drugs that boost S1P to treat or prevent coronary artery disease, the researchers concluded.
The work reported in this story was supported by the National Heart, Lung, and Blood Institute, part of the National Institutes of Health, through grant numbers R01HL126913 and R01HL152195 and a Harold S. Geneen Charitable Trust Award for Coronary Heart Disease Research.

People who take acid-reducing drugs may have a higher risk of migraine and other severe headache than people who do not take these medications, according to a study published in the April 24, 2024, online issue of Neurology®Clinical Practice, an official journal of the American Academy of Neurology. The acid-reducing drugs includeproton pump inhibitors such as omeprazole and esomeprazole, histamine H2-receptor antagonists, or H2 blockers, such as cimetidine and famotidine, and antacid supplements.
The study does not prove that acid-reducing drugs cause migraine; it only shows an association.
Acid reflux is when stomach acid flows into the esophagus, usually after a meal or when lying down. People with acid reflux may experience heartburn and ulcers. People with frequent acid reflux may develop gastroesophageal reflux disease, or GERD, which can lead to cancer of the esophagus.
“Given the wide usage of acid-reducing drugs and these potential implications with migraine, these results warrant further investigation,” said study author Margaret Slavin, PhD, RDN, of the University of Maryland in College Park. “These drugs are often considered to be overprescribed, and new research has shown other risks tied to long-term use of proton pump inhibitors, such as an increased risk of dementia.”
For the study, researchers looked at data on 11,818 people who provided information on use of acid-reducing drugs and whether they had migraine or severe headache in the past three months.
A total of 25% of participants taking proton pump inhibitors had migraine or severe headache, compared to 19% of those who were not taking the drugs. A total of 25% of those taking H2 blockers had severe headache, compared to 20% of those who were not taking those drugs. And 22% of those taking antacid supplements had severe headache, compared to 20% of those not taking antacids.
When researchers adjusted for other factors that could affect the risk of migraine, such as age, sex and use of caffeine and alcohol, they found that people taking proton pump inhibitors were 70% more likely to have migraine than people not taking proton pump inhibitors. Those taking H2 blockers were 40% more likely and those taking antacid supplements were 30% more likely.

“It’s important to note that many people do need acid-reducing medications to manage acid reflux or other conditions, and people with migraine or severe headache who are taking these drugs or supplements should talk with their doctors about whether they should continue,” Slavin said.
Slavin noted that the study looked only at prescription drugs. Some of the drugs became available for over-the-counter use at non-prescription strength during the study period, but use of these over-the-counter drugs was not included in this study.
Other studies have shown that people with gastrointestinal conditions may be more likely to have migraine, but Slavin said that relationship is not likely to fully explain the tie between acid-reducing drugs and migraine found in the study.
A limitation of the study is that a small number of people were taking the drugs, especially the H2 blockers.

Immigrants to Canada who have spent a greater proportion of their lives in Canada have a greater risk of developing multiple sclerosis (MS) than people who have spent a smaller proportion of their lives there, according to a study published in the April 24, 2024, online issue of Neurology®, the medical journal of the American Academy of Neurology. The study does not prove that an increased proportion of life in Canada causes MS; it only shows an association.
“Other studies have shown that immigrants tend to have better health than long-term residents, which is thought to be because healthy people are more likely to choose to immigrate,” said study author Manav V. Vyas, MBBS, MSc, PhD, of St. Michael’s Hospital in Toronto, Canada and a member of the American Academy of Neurology. “We wanted to see if the lower risk of MS declines over time as people adopt some of the unhealthy lifestyles of their new country or are exposed to other environmental factors that increase their risk.”
The study involved 1.5 million immigrants who arrived in Canada between 1985 and 2003 and were covered by health insurance for at least two years with no diagnosis of MS. The people were then followed through 2016.
During that time, 934 people were diagnosed with MS. This is a rate of 0.44 cases per 100,000 person-years. The overall rate of MS in Canada based on previous research is estimated to be 15 to 17 cases per 100,000 person-years. Person-years represent both the number of people in the study and the amount of time each person spends in the study.
The person’s age at arrival in Canada and the amount of time since they immigrated were used to determine the proportion of life spent in Canada. Overall, people had spent an average of 20% of their lives in Canada.
Researchers found that people who had spent 70% of their lives in Canada were 38% more likely to develop MS than people who had spent 20% of their lives there. This result took into account other factors that could affect the risk of MS, such as sex, age and other health conditions.
The researchers did not find any differences between men and women or based on which of Canada’s immigration classes people belonged to: family, refugee or economic.
“Our data did not include information on various environmental factors associated with MS, but our theories include that this increase in the risk of MS over time may be due to lifestyle factors such as higher rates of smoking and changes in diet, environmental factors such as sunlight exposure and biological factors such as the composition of the gut microbiome that have been previously associated with an increased risk of MS,” Vyas said. “Some immigrants may be more susceptible to these risk factors due to social determinants of health such as income, education, neighborhood and access to nutritious food.”
A limitation of the study is that new cases of MS were determined by use of the health care system, and immigrants may differ from non-immigrants in seeking care for their symptoms by cultural background, age, time spent in the country, familiarity with language or other factorsrelated to the health care system.
The study was supported by the MS Society of Canada and the Consortium of Multiple Sclerosis Centers.

When cancer patients undergo chemotherapy, the dose of most drugs is calculated based on the patient’s body surface area. This is estimated by plugging the patient’s height and weight into an equation, dating to 1916, that was formulated from data on just nine patients.
This simplistic dosing doesn’t take into account other factors and can lead to patients receiving either too much or too little of a drug. As a result, some patients likely experience avoidable toxicity or insufficient benefit from the chemotherapy they receive.
To make chemotherapy dosing more accurate, MIT engineers have come up with an alternative approach that can enable the dose to be personalized to the patient. Their system measures how much drug is in the patient’s system, and these measurements are fed into a controller that can adjust the infusion rate accordingly.
This approach could help to compensate for differences in drug pharmacokinetics caused by body composition, genetic makeup, chemotherapy-induced toxicity of the organs that metabolize the drugs, interactions with other medications being taken and foods consumed, and circadian fluctuations in the enzymes responsible for breaking down chemotherapy drugs, the researchers say.
“Recognizing the advances in our understanding of how drugs are metabolized, and applying engineering tools to facilitate personalized dosing, we believe, can help transform the safety and efficacy of many drugs,” says Giovanni Traverso, an associate professor of mechanical engineering at MIT, a gastroenterologist at Brigham and Women’s Hospital, and the senior author of the study.
Louis DeRidder, an MIT graduate student, is the lead author of the paper, which appears today in the journal Med.
Continuous monitoring
In this study, the researchers focused on a drug called 5-fluorouracil, which is used to treat colorectal cancers, among others. The drug is typically infused over a 46-hour period, and the dosage is determined using a formula based on the patient’s height and weight, which gives the estimated body surface area.

However, that approach doesn’t account for differences in body composition that can affect how the drug spreads through the body, or genetic variations that influence how it is metabolized. Those differences can lead to harmful side effects, if too much drug is present. If not enough drug is circulating, it may not kill the tumor as expected.
“People with the same body surface area could have very different heights and weights, could have very different muscle masses or genetics, but as long as the height and the weight plugged into this equation give the same body surface area, their dose is identical,” says DeRidder, a PhD candidate in the Medical Engineering and Medical Physics program within the Harvard-MIT Program in Health Sciences and Technology.
Another factor that can alter the amount of drug in the bloodstream at any given time is circadian fluctuations of an enzyme called dihydropyrimidine dehydrogenase (DPD), which breaks down 5-fluorouracil. DPD’s expression, like many other enzymes in the body, is regulated on a circadian rhythm. Thus, the degradation of 5-FU by DPD is not constant but changes according to the time of the day. These circadian rhythms can lead to tenfold fluctuations in the amount of 5-fluorouracil in a patient’s bloodstream over the course of an infusion.
“Using body surface area to calculate a chemotherapy dose, we know that two people can have profoundly different toxicity from 5-fluorouracil chemotherapy. Looking at one patient, they can have cycles of treatment with minimal toxicity and then have a cycle with miserable toxicity. Something changed in how that patient metabolized chemo from one cycle to the next. Our antiquated dosing fails to capture that change, and patients suffer as a result,” says Douglas Rubinson, a clinical oncologist at Dana-Farber Cancer Institute and an author of the paper.
One way to try to counteract the variability in chemotherapy pharmacokinetics is a strategy called therapeutic drug monitoring, in which the patient gives a blood sample at the end of one treatment cycle. After this sample is analyzed for the drug concentration, the dosage can be adjusted, if needed, at the beginning of the next cycle (usually two weeks later for 5-fluorouracil). This approach has been shown to result in better outcomes for patients, but it is not widely used for chemotherapies such as 5-fluorouracil.
The MIT researchers wanted to develop a similar type of monitoring, but in a manner that is automated and enables real-time drug personalization, which could result in better outcomes for patients. In their “closed-loop” system, drug concentrations can be continually monitored, and that information is used to automatically adjust the infusion rate of the chemotherapy drug and keep the dose within the target range. Such a closed-loop system enables personalization of the drug dose in a manner that considers circadian rhythm changes in the levels of drug-metabolizing enzymes, as well as any changes in the patient’s pharmacokinetics since their last treatment, such as chemotherapy-induced toxicity of the organs that metabolize the drugs.

The new system they designed, known as CLAUDIA (Closed-Loop AUtomated Drug Infusion regulAtor), makes use of commercially available equipment for each step. Blood samples are taken every five minutes and rapidly prepared for analysis. The concentration of 5-fluorouracil in the blood is measured and compared to the target range. The difference between the target and measured concentration is input to a control algorithm, which then adjusts the infusion rate if necessary, to keep the dose within the range of concentrations between which the drug is effective and nontoxic.
“What we’ve developed is a system where you can constantly measure the concentration of drug and adjust the infusion rate accordingly, to keep the drug concentration within the therapeutic window,” DeRidder says.
Rapid adjustment
In tests in animals, the researchers found that using CLAUDIA, they could keep the amount of drug circulating in the body within the target range around 45 percent of the time. Drug levels in animals that received chemotherapy without CLAUDIA remained in the target range only 13 percent of the time, on average. In this study, the researchers did not do any tests of the effectiveness of the drug levels, but keeping the concentration within the target window is believed to lead to better outcomes and less toxicity.
CLAUDIA was also able to keep the dose of 5-fluorouracil within the target range even when the researchers administered a drug that inhibits the DPD enzyme. In animals that received this inhibitor without continuous monitoring and adjustment, levels of 5-fluorouracil increased by up to eightfold.
For this demonstration, the researchers manually performed each step of the process, using off-the-shelf equipment, but they now plan to work on automating each step so that the monitoring and dose adjustment can be done without any human intervention.
To measure drug concentrations, the researchers used high-performance liquid chromatography mass spectroscopy (HPLC-MS), a technique that could be adapted to detect nearly any type of drug.
“We foresee a future where we’re able to use CLAUDIA for any drug that has the right pharmacokinetic properties and is detectable with HPLC-MS, thereby enabling the personalization of dosing for many different drugs,” DeRidder says.
The research was funded by the National Science Foundation Graduate Research Fellowship Program, a MathWorks Fellowship, MIT’s Karl van Tassel Career Development Professorship, the MIT Department of Mechanical Engineering, and the Bridge Project, a partnership between the Koch Institute for Integrative Cancer Research at MIT and the Dana-Farber/Harvard Cancer Center.
Other authors of the paper include Kyle A. Hare, Aaron Lopes, Josh Jenkins, Nina Fitzgerald, Emmeline MacPherson, Niora Fabian, Josh Morimoto, Jacqueline N. Chu, Ameya R. Kirtane, Wiam Madani, Keiko Ishida, Johannes L. P. Kuosmanen, Naomi Zecharias, Christopher M. Colangelo, Hen-Wei Huang, Makaya Chilekwa, Nikhil B. Lal, Shriya S. Srinivasan, Alison M Hayward, Brian M. Wolpin, David Trumper, Troy Quast, and Robert Langer.

Pivmecillinam, which has been used in Europe for decades, will become available next year to women 18 and older.The Food and Drug Administration on Wednesday approved the sale of an antibiotic for the treatment of urinary tract infections in women, giving U.S. health providers a powerful new tool to combat a common infection that is increasingly unresponsive to the existing suite of antimicrobial drugs.The drug, pivmecillinam, has been used in Europe for more than 40 years, where it is often a first-line therapy for women with uncomplicated U.T.I.’s, meaning the infection is confined to the bladder and has not reached the kidneys. The drug will be marketed in the U.S. as Pivya and will be made available by prescription to women 18 and older.It is the first time in two decades that the F.D.A. has approved a new antibiotic for U.T.I.s, which annually affect 30 million Americans. U.T.I.s are responsible for the single-greatest use of antibiotics outside a hospital setting.“Uncomplicated U.T.I.s are a very common condition impacting women and one of the most frequent reasons for antibiotic use,” Dr. Peter Kim, director of the Division of Anti-Infectives at the F.D.A.’s Center for Drug Evaluation and Research, said in a statement. “The F.D.A. is committed to fostering new antibiotic availability when they prove to be safe and effective.”Utility Therapeutics, the U.S. company that acquired the rights to pivmecillinam, said it would be available in 2025. The company is also seeking F.D.A. approval for an intravenous version of the drug that is used for more serious infections and is usually administered in a hospital setting.Health practitioners said they were elated to have another tool in their arsenal given the growing challenge of antimicrobial resistance, which makes existing medications less effective as pathogens mutate in ways that allow them to survive a course of antibiotics.We are having trouble retrieving the article content.Please enable JavaScript in your browser settings.Thank you for your patience while we verify access. If you are in Reader mode please exit and log into your Times account, or subscribe for all of The Times.Thank you for your patience while we verify access.Already a subscriber? Log in.Want all of The Times? Subscribe.

Tumors actively prevent the formation of immune responses by so-called cytotoxic T cells, which are essential in combating cancer. Researchers at the Technical University of Munich (TUM) and the Ludwig-Maximilians-Universität München (LMU) Hospital have now uncovered for the first time how this exactly happens. The study in the journal Nature provides rationales for new cancer immunotherapies and could make existing treatments more effective. A second paper in Nature confirms the findings.
In cancer, tumors often impair the body’s immune response. For example, they can prevent immune cells from perceiving cancer cells as a threat or render them inactive. Immunotherapies aim to overcome these mechanisms and stimulate the immune system, in particular the T cells. However, such therapies do not work for a large number of cancer patients. Researchers around the world are looking for the causes and new counter-strategies.
Messenger substance stops effector development of T cells in tumors
A team led by Dr. Jan Böttcher, research group leader at the Institute of Molecular Immunology at TUM, and Prof. Sebastian Kobold, Deputy Director of the Department of Clinical Pharmacology at LMU Klinikum München, has now discovered that tumors use a messenger substance to influence immune cells in an early phase of the immune response. Many cancer cells show increased secretion of the messenger substance prostaglandin E2. The researchers were able to show that prostaglandin E2 binds to EP2 and EP4, two receptors on the surface of certain immune cells.
These so-called stem-like T cells migrate from other areas of the body into the tumor. If the immune response is successful, they multiply in the tumor and develop into cytotoxic T cells that attack the cancer. “This whole process is strongly limited when tumors secrete prostaglandin E2 and this factor binds to EP2 and EP4 receptors,” says Jan Böttcher. “The T cell response collapses and the tumor can progress.” If the researchers prevented the interaction of messenger substance and receptor in tumor models, the immune system was able to fight tumors effectively.
Current therapies address a later point of the immune response
“We have discovered a mechanism that influences the body’s immune response in a crucial phase,” says Jan Böttcher. “Many tumors prevent the stem-like T cells from generating cytotoxic T cells in the tumor that could attack the cancer.”
Current immunotherapies aim to prevent the cancer from switching off immune responses at a later phase. Checkpoint inhibitor therapies, for example, aim to release the blockade of fully differentiated cytotoxic T cells and “switch them back on.” Before the dreaded T cell exhaustion sets in, which other researchers are trying to prevent, differentiated T cells must also be present.

Increase the effectiveness of existing therapies
“Current treatment approaches would probably be more effective if the effects of prostaglandin E2 on stem-like T cells is blocked to enable their unhindered differentiation within tumor tissue,” says Sebastian Kobold.
This similarly applies to recent approaches that rely on the protein IL-2 to stimulate T cells. The current study shows that as soon as the prostaglandin E2 binds to the two receptors, T cells can no longer respond to IL-2. “We suspect that even the body’s own IL-2 signals may be sufficient to enable T cells to successfully fight cancer once the effects of prostaglandin E2 have been stopped,” says Sebastian Kobold.
Second study in “Nature” confirms results
A second research publication in Nature investigates the effects of prostaglandin E2 on the immune system. For this study, the authors, researchers from the University Hospital of Lausanne, collaborated with the Munich team. In their laboratory, they among other things examined T cells from human tumor tissue. When they blocked the release of prostaglandin E2 in cancer tissue, the T cells showed better expansion and were thus able to fight human cancer cells more effectively.
Search for counter-strategies begins
“We now have a concrete starting point for significantly improving immunotherapies,” says Jan Böttcher. “Researchers around the world must now develop strategies to overcome the tumors’ defense. We need to stop the effects of prostaglandin E2 — either by preventing tumors from producing the molecule or by making immune cells resistant to it.”

As our battle against cancer rages on, the quest for more sophisticated and realistic models to study tumor development has never been more critical. Until now, research has relied on animal models and simplified cell culture methods, which are valuable but cannot fully capture the complex interplay of factors involved in tumor development.
Even newer, more advanced models for studying cancer, such as organoids — tiny, lab-grown versions of organs — do not faithfully replicate the cell behaviors and tissue architectures seen in actual tumors.
This gap has significantly hindered our understanding of the intricate processes underlying cancer initiation, progression, and response to treatment, and calls for more sophisticated models to accurately mimic the disease’s complexity.
In a significant leap forward for cancer modeling, scientists have combined microfabrication and tissue engineering techniques to develop miniature colon tissues that can simulate the complex process of tumorigenesis outside the body with high fidelity, giving rise to tumors that closely resemble those found in vivo.
The breakthrough, now published in Nature, was made by Luis Francisco Lorenzo Martín, Tania Hübscher and other members of the group of Matthias Lütolf at EPFL, with input from the group of Freddy Radtke (EPFL) and colleagues at Roche’s Institute of Human Biology.
The mini-colons are topobiologically complex, meaning that they not only replicate the physical structure of colon tissue, including its distinctive crypt-and-lumen architecture, but they also mimic the cellular diversity present in the actual colon tissue during healthy and diseased states.
Optogenetics: Turning cancer “on”
Another important feature of the mini-colons is that they can be induced to develop tumors “at will” and in targeted areas — a massive advantage for cancer research. The researchers were able to turn inducible oncogenic genes on using “optogenetics.” This cutting-edge technique uses light to control biological processes such as gene expression.

By integrating a blue-light-responsive system into the mini-colons, the researchers made them undergo controlled oncogenic mutations, which can reveal tumor evolution with unprecedented details. This optogenetic approach allowed the scientists to induce targeted changes in specific cell populations within the mini-colons, mimicking the localized onset of colorectal cancer in the body.
“In essence, we used light to trigger tumorigenesis by turning on oncogenic driver mutations in a spatiotemporally controlled manner in healthy bioengineered colon epithelial organoids,” says Matthias Lütolf, who is also the founding director of Roche’s new Institute of Human Biology. “This basically allows you to watch tumor formation in real-time and do very detailed analyses of a process that’s very difficult to study in a mouse.”
The ability to trigger these genetic changes with light in the miniature colons not only allows more controlled and more precise activation of the oncogenes, but also provides a powerful tool to study the dynamic processes of tumor development and the cellular response to these mutations in real-time. This innovative use of optogenetics opens up new possibilities for dissecting the molecular and cellular mechanisms of cancer.
By manipulating genetic and environmental conditions, the researchers were also able to replicate and observe a range of tumor behaviors in the mini-colons, and even identified key factors influencing cancer progression — for example, the protein GPX2, which associated with stem cell characteristics and tumor growth.
This groundbreaking research offers a potent new tool for exploring the underlying mechanisms of colorectal cancer and testing potential therapies, particularly when applied to human patient-derived tissues. The mini-colons’ ability to mimic tumor dynamics can reduce our reliance on animal models, which can accelerate the discovery and development of effective treatments.