“The same particles in the air that derive from the combustion of fossil fuels, exacerbating climate change, are directly impacting human health via an important and previously overlooked cancer-causing mechanism in lung cells. The risk of lung cancer from air pollution is lower than from smoking, but we have no control over what we all breathe. Globally, more people are exposed to unsafe levels of air pollution than to toxic chemicals in cigarette smoke, and these new data link the importance of addressing climate health to improving human health,” said Charles Swanton, the Francis Crick Institute and Cancer Research UK Chief Clinician, London, UK, who will present the research results at the ESMO 2022 Presidential Symposium on Saturday, 10 September.

The new findings are based on human and laboratory research on mutations in a gene called EGFR which are seen in about half of people with lung cancer who have never smoked. In a study of nearly half a million people living in England, South Korea and Taiwan, exposure to increasing concentrations of airborne particulate matter (PM) 2.5 micrometres (μm) in diameter was linked to increased risk of NSCLC with EGFR mutations.

In the laboratory studies, the Francis Crick Institute scientists showed that the same pollutant particles (PM2.5) promoted rapid changes in airway cells which had mutations in EGFR and in another gene linked to lung cancer called KRAS, driving them towards a cancer stem cell like state. They also found that air pollution drives the influx of macrophages which release the inflammatory mediator, interleukin-1β, driving the expansion of cells with the EGFR mutations in response to exposure to PM2.5, and that blockade of interleukin-1β inhibited lung cancer initiation. These findings were consistent with data from a previous large clinical trial showing a dose dependent reduction in lung cancer incidence when people were treated with the anti-IL1β antibody, canakinumab (4).

In a final series of experiments, the Francis Crick team used state-of-the-art, ultradeep mutational profiling of small samples of normal lung tissue and found EGFR and KRAS driver mutations in 18% and 33% of normal lung samples, respectively.

“We found that driver mutations in EGFR and KRAS genes, commonly found in lung cancers, are actually present in normal lung tissue and are a likely consequence of ageing. In our research, these mutations alone only weakly potentiated cancer in laboratory models. However, when lung cells with these mutations were exposed to air pollutants, we saw more cancers and these occurred more quickly than when lung cells with these mutations were not exposed to pollutants, suggesting that air pollution promotes the initiation of lung cancer in cells harbouring driver gene mutations. The next step is to discover why some lung cells with mutations become cancerous when exposed to pollutants while others don’t,” said Swanton.

Commenting on the results, Tony Mok, Chinese University of Hong Kong, not involved in the study, said: “This research is intriguing and exciting as it means that we can ask whether, in the future, it will be possible to use lung scans to look for pre-cancerous lesions in the lungs and try to reverse them with medicines such as interleukin-1β inhibitors. We don’t yet know whether it will be possible to use highly sensitive EGFR profiling on blood or other samples to find non-smokers who are predisposed to lung cancer and may benefit from lung scanning, so discussions are still very speculative.”

Like Swanton, he stresses the importance of reducing air pollution to lower the risk of lung diseases, including cancer. “We have known about the link between pollution and lung cancer for a long time, and we now have a possible explanation for it. As consumption of fossil fuels goes hand in hand with pollution and carbon emissions, we have a strong mandate for tackling these issues — for both environmental and health reasons,” Mok concluded.A new mechanism has been identified through which very small pollutant particles in the air may trigger lung cancer in people who have never smoked, paving the way to new prevention approaches and development of therapies, according to late-breaking data [to be] reported at the ESMO Congress 2022 by scientists of the Francis Crick Institute and University College London, funded by Cancer Research UK (1). The particles, which are typically found in vehicle exhaust and smoke from fossil fuels, are associated with non-small cell lung cancer (NSCLC) risk, accounting for over 250,000 lung cancer deaths globally per year (2,3).

“The same particles in the air that derive from the combustion of fossil fuels, exacerbating climate change, are directly impacting human health via an important and previously overlooked cancer-causing mechanism in lung cells. The risk of lung cancer from air pollution is lower than from smoking, but we have no control over what we all breathe. Globally, more people are exposed to unsafe levels of air pollution than to toxic chemicals in cigarette smoke, and these new data link the importance of addressing climate health to improving human health,” said Charles Swanton, the Francis Crick Institute and Cancer Research UK Chief Clinician, London, UK, who will present the research results at the ESMO 2022 Presidential Symposium on Saturday, 10 September.

The new findings are based on human and laboratory research on mutations in a gene called EGFR which are seen in about half of people with lung cancer who have never smoked. In a study of nearly half a million people living in England, South Korea and Taiwan, exposure to increasing concentrations of airborne particulate matter (PM) 2.5 micrometres (μm) in diameter was linked to increased risk of NSCLC with EGFR mutations.

In the laboratory studies, the Francis Crick Institute scientists showed that the same pollutant particles (PM2.5) promoted rapid changes in airway cells which had mutations in EGFR and in another gene linked to lung cancer called KRAS, driving them towards a cancer stem cell like state. They also found that air pollution drives the influx of macrophages which release the inflammatory mediator, interleukin-1β, driving the expansion of cells with the EGFR mutations in response to exposure to PM2.5, and that blockade of interleukin-1β inhibited lung cancer initiation. These findings were consistent with data from a previous large clinical trial showing a dose dependent reduction in lung cancer incidence when people were treated with the anti-IL1β antibody, canakinumab (4).

In a final series of experiments, the Francis Crick team used state-of-the-art, ultradeep mutational profiling of small samples of normal lung tissue and found EGFR and KRAS driver mutations in 18% and 33% of normal lung samples, respectively.

“We found that driver mutations in EGFR and KRAS genes, commonly found in lung cancers, are actually present in normal lung tissue and are a likely consequence of ageing. In our research, these mutations alone only weakly potentiated cancer in laboratory models. However, when lung cells with these mutations were exposed to air pollutants, we saw more cancers and these occurred more quickly than when lung cells with these mutations were not exposed to pollutants, suggesting that air pollution promotes the initiation of lung cancer in cells harbouring driver gene mutations. The next step is to discover why some lung cells with mutations become cancerous when exposed to pollutants while others don’t,” said Swanton.

Commenting on the results, Tony Mok, Chinese University of Hong Kong, not involved in the study, said: “This research is intriguing and exciting as it means that we can ask whether, in the future, it will be possible to use lung scans to look for pre-cancerous lesions in the lungs and try to reverse them with medicines such as interleukin-1β inhibitors. We don’t yet know whether it will be possible to use highly sensitive EGFR profiling on blood or other samples to find non-smokers who are predisposed to lung cancer and may benefit from lung scanning, so discussions are still very speculative.”

Like Swanton, he stresses the importance of reducing air pollution to lower the risk of lung diseases, including cancer.

“We have known about the link between pollution and lung cancer for a long time, and we now have a possible explanation for it. As consumption of fossil fuels goes hand in hand with pollution and carbon emissions, we have a strong mandate for tackling these issues — for both environmental and health reasons,” Mok concluded.

References

1. LBA1 ‘Mechanism of action and an actionable inflammatory axis for air pollution induced non-small cell lung cancer in never smokers’ will be presented by Charles Swanton during Presidential Symposium 1 on 10 September. Annals of Oncology, Volume 33 Supplement 7, September 2022
2. Liu X, Mubarik S, Wang S. Lung Cancer Death Attributable to Long-Term Ambient Particulate Matter (PM_2.5) Exposure in East Asian Countries During 1990-2019. Frontiers in Medicine 2021 Oct 15;8:742076
3. Turner MC, Andersen ZJ, Baccarelli A et al. Outdoor Air Pollution and Cancer: An Overview of the Current Evidence and Public Health Recommendations. CA: Cancer J Clin 2020; 70: 460-479
4. Ridker PM, MacFadyen JG, Thuren T et al. Effect of interleukin-1β inhibition with canakinumab on incident lung cancer in patients with atherosclerosis: exploratory results from a randomised, double-blind, placebo-controlled trial. Lancet 2017 Oct 21; 390 (10105): 1833-1842

“I absolutely believe in the power of ML but it has to be a relevant addition,” said neurosurgeon-in-training and statistics editor Dr Victor Volovici, first author of the comment, from Erasmus MC University Medical Center, The Netherlands. “Sometimes ML algorithms do not perform better than traditional statistical methods, leading to the publication of papers that lack clinical or scientific value.”

Real world examples have shown that the misuse of algorithms in healthcare could perpetuate human prejudices or inadvertently cause harm when the machines are trained on biased datasets.

“Many believe ML will revolutionise healthcare because machines make choices more objectively than humans. But without proper oversight, ML models may do more harm than good,” said Associate Professor Nan Liu, senior author of the comment, from the Centre for Quantitative Medicine and Health Services & Systems Research Programme at Duke-NUS Medical School, Singapore.

“If, through ML, we uncover patterns that we otherwise would not see — like in radiology and pathology images — we should be able to explain how the algorithms got there, to allow for checks and balances.”

Together with a group of scientists from the UK and Singapore, the researchers highlight that although guidelines have been formulated to regulate the use of ML in clinical research, these guidelines are only applicable once a decision to use ML has been made and do not ask whether or when its use is appropriate in the first place.

For example, companies have successfully trained ML algorithms to recognise faces and road objects using billions of images and videos. But when it comes to their use in healthcare settings, they are often trained on data in the tens, hundreds or thousands. “This underscores the relative poverty of big data in healthcare and the importance of working towards achieving sample sizes that have been attained in other industries, as well as the importance of a concerted, international big data sharing effort for health data,” the researchers write.

Another issue is that most ML and deep learning algorithms (that do not receive explicit instructions regarding the outcome) are often still regarded as a ‘black box’. For example, at the start of the COVID-19 pandemic, scientists published an algorithm that could predict coronavirus infections from lung photos. Afterwards, it turned out that the algorithm had drawn conclusions based on the imprint of the letter ‘R’ (for ‘Right Lung’) in the photos, which was always found in a slightly different spot on the scans.

“We have to get rid of the idea that ML can discover patterns in data that we cannot understand,” said Dr Volovici about the incident. “ML can very well discover patterns that we cannot see directly, but then you have to be able to explain how you came to that conclusion. In order to do that, the algorithm has to be able to show what steps it took, and that requires innovation.”

The researchers advise that ML algorithms should be evaluated against traditional statistical approaches (when applicable) before they are used in clinical research. And when deemed appropriate, they should complement clinician decision-making, rather than replace it. “ML researchers should recognise the limits of their algorithms and models in order to prevent their overuse and misuse, which could otherwise sow distrust and cause patient harm,” the researchers write.

The team is working on organising an international effort to provide guidance on the use of ML and traditional statistics, and also to set up a large database of anonymised clinical data that can harness the power of ML algorithms.

Story Source:

Materials provided by Duke-NUS Medical School. Note: Content may be edited for style and length.

Scientists at Sandia National Laboratories and the Max Planck Institute for the Science of Light have reported on a device that could replace a roomful of equipment to link photons in a bizarre quantum effect called entanglement. This device — a kind of nano-engineered material called a metasurface — paves the way for entangling photons in complex ways that have not been possible with compact technologies.

When scientists say photons are entangled, they mean they are linked in such a way that actions on one affect the other, no matter where or how far apart the photons are in the universe. It is an effect of quantum mechanics, the laws of physics that govern particles and other very tiny things.

Although the phenomenon might seem odd, scientists have harnessed it to process information in new ways. For example, entanglement helps protect delicate quantum information and correct errors in quantum computing, a field that could someday have sweeping impacts in national security, science and finance. Entanglement is also enabling new, advanced encryption methods for secure communication.

Research for the groundbreaking device, which is a hundred times thinner than a sheet of paper, was performed, in part, at the Center for Integrated Nanotechnologies, a Department of Energy Office of Science user facility operated by Sandia and Los Alamos national laboratories. Sandia’s team received funding from the Office of Science, Basic Energy Sciences program.

Light goes in, entangled photons come out

The new metasurface acts as a doorway to this unusual quantum phenomenon. In some ways, it’s like the mirror in Lewis Carrol’s “Through the Looking-Glass,” through which the young protagonist Alice experiences a strange, new world.

Instead of walking through their new device, scientists shine a laser through it. The beam of light passes through an ultrathin sample of glass covered in nanoscale structures made of a common semiconductor material called gallium arsenide.

“It scrambles all the optical fields,” said Sandia senior scientist Igal Brener, an expert in a field called nonlinear optics who led the Sandia team. Occasionally, he said, a pair of entangled photons at different wavelengths emerge from the sample in the same direction as the incoming laser beam.

Brener said he is excited about this device because it is designed to produce complex webs of entangled photons — not just one pair at a time, but several pairs all entangled together, and some that can be indistinguishable from each other. Some technologies need these complex varieties of so-called multi-entanglement for sophisticated information processing schemes.

Other miniature technologies based on silicon photonics can also entangle photons but without the much-needed level of complex, multi-entanglement. Until now, the only way to produce such results was with multiple tables full of lasers, specialized crystals and other optical equipment.

“It is quite complicated and kind of intractable when this multi-entanglement needs more than two or three pairs,” Brener said. “These nonlinear metasurfaces essentially achieve this task in one sample when before it would have required incredibly complex optical setups.”

The Science paper outlines how the team successfully tuned their metasurface to produce entangled photons with varying wavelengths, a critical precursor to generating several pairs of intricately entangled photons simultaneously.

However, the researchers note in their paper that the efficiency of their device — the rate at which they can generate groups of entangled photons — is lower than that of other techniques and needs to be improved.

What is a metasurface?

A metasurface is a synthetic material that interacts with light and other electromagnetic waves in ways conventional materials can’t. Commercial industries, said Brener, are busy developing metasurfaces because they take up less space and can do more with light than, for instance, a traditional lens.

“You now can replace lenses and thick optical elements with metasurfaces,” Brener said. “Those types of metasurfaces will revolutionize consumer products.”

Sandia is one of the leading institutions in the world performing research in metasurfaces and metamaterials. Between its Microsystems Engineering, Science and Applications complex, which manufactures compound semiconductors, and the nearby Center for Integrated Nanotechnologies, researchers have access to all the specialized tools they need to design, fabricate and analyze these ambitious new materials.

“The work was challenging as it required precise nanofabrication technology to obtain the sharp, narrowband optical resonances that seeds the quantum process of the work,” said Sylvain Gennaro, a former postdoctoral researcher at Sandia who worked on several aspects of the project.

The device was designed, fabricated and tested through a partnership between Sandia and a research group led by physicist Maria Chekhova, an expert in the quantum entanglement of photons at the Max Planck Institute for the Science of Light.

“Metasurfaces are leading to a paradigm shift in quantum optics, combining ultrasmall sources of quantum light with far reaching possibilities for quantum state engineering,” said Tomás Santiago-Cruz, a member of the Max Plank team and first author on the paper.

Brener, who has studied metamaterials for more than a decade, said this newest research could possibly spark a second revolution — one that sees these materials developed not just as a new kind of lens, but as a technology for quantum information processing and other new applications.

“There was one wave with metasurfaces that is already well established and on its way. Maybe there is a second wave of innovative applications coming,” he said

Sandia National Laboratories is a multimission laboratory operated by National Technology and Engineering Solutions of Sandia LLC, a wholly owned subsidiary of Honeywell International Inc., for the U.S. Department of Energy’s National Nuclear Security Administration. Sandia Labs has major research and development responsibilities in nuclear deterrence, global security, defense, energy technologies and economic competitiveness, with main facilities in Albuquerque, New Mexico, and Livermore, California.