(Press-News.org) Not all cancerous tumors are created equal. Some tumors, known as "hot" tumors, show signs of inflammation, which means they are infiltrated with T cells working to fight the cancer. Those tumors are easier to treat, as immunotherapy drugs can then amp up the immune response.
"Cold" tumors, on the other hand, have no T-cell infiltration, which means the immune system is not stepping in to help. With these tumors, immunotherapy is of little use.
It's the latter type of tumor that researchers Michael Knitz and radiation oncologist and University of Colorado Cancer Center member Sana Karam, MD, PhD, address in new research published this week in the Journal for ImmunoTherapy of Cancer. Working with mouse models in Karam's specialty area of head and neck cancers, Knitz and Karam studied the role of T cells in tumor treatment.
"What we found is that the cells that normally tell the T cell, 'Hey, here's a tumor -- come and attack it,' are being silenced," Karam says.
She and her team found that regulatory T cells (Tregs), a specialized T cell type that suppresses immune response, are essentially telling the T cells to stop fighting the cancer.
"Tregs normally serve as an important balance in a healthy immune system," Knitz says. "They prevent autoimmune disease and put the brakes on the T cells when needed. However, in many tumors, Tregs are too numerous or overly suppressive, bringing the T cell response to a halt."
Using medication that deactivates the Tregs can help boost the immune response in patients with cold tumors, the researchers found, as can radiation treatment that causes enough injury that the immune cells known as dendritic cells work to put the regular T cells into fight mode.
But this is only part of the story. The T cells need to know what to attack. "You need the radiation to create injury and bring in the immune cells so that the tumor can be recognized and targeted," says Karam, also an associate professor of radiation oncology at the University of Colorado School of Medicine. "That way, the dendritic cells trigger the immune system to produce a lot of T cells, similar to what a vaccine does. Those T cells then go back to the tumor to kill cancer cells. The pieces are already in place; they just need the proper signals. Activating the dendritic cells is a crucial step in allowing radiation to heat up these cold tumors."
Importantly, Karam and her team, which includes post-doctorate fellow Thomas Bickett, found that the radiation must be administered in a specific way.
"A specific dosing is needed," Karam says. "You have to pulse it. You can't just give one dose. You have to give it again and combine it with things that remove the suppression -- the Tregs -- while simultaneously keeping those antigen-presenting dendritic cells active and on board."
Karam says the next step in her research is clinical trials she hopes will eventually change the treatment paradigm from surgery and weeks of chemotherapy and radiation to just three sessions of radiation and immunotherapy, then surgery. She is driven to change the standard of care for cold tumors, she explains, because of the horrendous effects they have on patients.
"These tumors resemble those in patients who are heavy smokers," she says. "They're very destructive to bone and muscle, infiltrating the tongue, jaw, gum, and lymph nodes. It's horrible. We have very high failure rates with them, and the treatment often involves removing the tongue and weeks of radiation and chemotherapy, only for the patient to fail. I'm confident that we can do better for our patients."
INFORMATION:
PROVIDENCE, R.I. [Brown University] -- As NASA's Perseverance rover begins its search for ancient life on the surface of Mars, a new study suggests that the Martian subsurface might be a good place to look for possible present-day life on the Red Planet.
The study, published in the journal Astrobiology, looked at the chemical composition of Martian meteorites -- rocks blasted off of the surface of Mars that eventually landed on Earth. The analysis determined that those rocks, if in consistent contact with water, would produce the chemical energy needed to support microbial communities similar to those that survive in the unlit depths of the Earth. Because these meteorites may be representative ...
The unprecedented development of COVID-19 vaccines less than a year after discovery of this virus was enabled by more than $17 billion of research on vaccine technologies funded by the NIH prior to the pandemic, according to new research from Bentley University's Center for Integration of Science and Industry. The article, titled "NIH funding for vaccine readiness before the COVID-19 pandemic," demonstrates the critical role this broad foundation of government-funded research plays in ensuring vaccine readiness.
The report, published today in the journal Vaccine, ...
DALLAS - April 22, 2021 - Being Black or Hispanic, living in high-poverty neighborhoods, and having Medicaid or no insurance coverage are associated with higher mortality in men and women under 40 with cancer, a review by UT Southwestern Medical Center researchers found.
"Survival is not different because of biology. It's not different because of patient-level factors," says Caitlin Murphy, Ph.D., lead author of the study and an assistant professor of population and data sciences and internal medicine at UT Southwestern. "No matter which way we looked at the data, we still saw consistent and alarming differences in survival by race - and these are teens and young adults."
Other findings based on an ...
Machine learning could provide up an extra hour of warning time for debris flows along the Illgraben torrent in Switzerland, researchers report at the Seismological Society of America (SSA)'s 2021 Annual Meeting.
Debris flows are mixtures of water, sediment and rock that move rapidly down steep hills, triggered by heavy precipitation and often containing tens of thousands of cubic meters of material. Their destructive potential makes it important to have monitoring and warning systems in place to protect nearby people and infrastructure.
In her presentation at SSA, Ma?gorzata Chmiel of ETH Zürich described a machine learning approach to detecting and alerting against debris flows for the Illgraben torrent, a site in the European Alps that experiences significant debris flows and torrential ...
It seems like a smooth slab of stainless steel, but look a little closer, and you'll see a simplified cross-section of the Los Angeles sedimentary basin.
Caltech researcher Sunyoung Park and her colleagues are printing 3D models like the metal Los Angeles proxy to provide a novel platform for seismic experiments. By printing a model that replicates a basin's edge or the rise and fall of a topographic feature and directing laser light at it, Park can simulate and record how seismic waves might pass through the real Earth.
In her presentation at the Seismological Society of America (SSA)'s 2021 Annual Meeting, Park explained why these physical models can address some of the drawbacks of numerical modeling of ground motion in some cases.
Small-scale, complex structures in ...
Days after the 4 August 2020 massive explosion at the port of Beirut in Lebanon, researchers were on the ground mapping the impacts of the explosion in the port and surrounding city.
The goal was to document and preserve data on structural and façade damage before rebuilding, said University of California, Los Angeles civil and environmental engineer Jonathan Stewart, who spoke about the effort at the Seismological Society of America (SSA)'s 2021 Annual Meeting.
The effort also provided an opportunity to compare NASA Jet Propulsion Laboratory satellite surveys of the blast effects with data collected from the ground surveys. Stewart and his colleagues concluded that satellite-based Damage Proxy Maps were effective at identifying severely damaged buildings and undamaged ...
Research has identified critical factors that enable dangerous bacteria to spread disease by surviving on surfaces in hospitals and kitchens.
The study into the mechanisms which enable the opportunistic human pathogen Pseudomonas aeruginosa to survive on surfaces, could lead to new ways of targeting harmful bacteria.
To survive outside their host, pathogenic bacteria must withstand various environmental stresses. One mechanism is the sugar molecule, trehalose, which is associated with a range of external stresses, particularly osmotic shock - sudden changes to the salt concentration surrounding cells.
Researchers ...
EUGENE, Ore. -- April 22, 2021 -- Product marketers should be clear in their messaging to avoid customer skepticism that makes them feel duped, according to University of Oregon research.
At issue in a new study, published in the Journal of Business Research, was a social-cognitive construct called theory of mind, which considers how well people assess the mental states and apparent goals of others.
Developmental psychologists link it to an ability to show empathy. In business, the study, led by former UO doctoral student Elizabeth Minton, showed it also can influence a person's recognition of being persuaded. And that affects a person's evaluation and willingness to buy a product, she found.
"There has been some research on adult theory of mind, particularly in understanding ...
Severity of illness, history of stroke, and being divorced or widowed were independently predictive of delirium in hospitalized patients in Zambia, according to a study published in PLOS ONE.
A collaborative team of researchers from Vanderbilt University Medical Center and the University of Zambia Teaching Hospital published the risk factors as a follow-up look at the prevalence and impact of delirium, a form of acute brain dysfunction, in lower-resourced hospitals. Findings published in February showed delirium is widespread in patients admitted to the University Teaching Hospital, and the duration of delirium predicted both mortality and disability at six months after discharge.
The studies represent ...
PHILADELPHIA -- (April 22, 2021) -- A synthetic DNA vaccine candidate for Middle East respiratory syndrome coronavirus (MERS-CoV) developed at The Wistar Institute induced potent immune responses and afforded protective efficacy in non-human primate (NHP) models when given intradermally in abbreviated, low-dose immunization regimen. A similar vaccine candidate was previously shown to be safe and tolerable with a three-dose intramuscular injection regimen in a recently completed human phase 1 study and is currently in expanded studies of phase 1/2a trial. ...
