In a small study, the scientists found that the immune cells in a majority of people with this deadly skin cancer fail to respond properly to a molecule called interferon, which normally activates the immune system. Without the ability to respond to interferon, the cells are less able to fend off the cancer, according to the study that will be published in the May issue of Public Library of Science-Medicine.
These results help explain a decade of research showing that people with cancer often have dysfunctional immune systems. Until now, researchers could tell that the immune system wasn't working properly but didn't know which genes or pathways were involved in that failure. Finding the disruption in the cancer cells' interferon response could help in the development of vaccines to treat cancers.
"We think this is a dominant way that immune dysfunction occurs in people with cancer," said senior author Peter Lee, MD, associate professor of medicine.
Lee was interested in melanoma rather than other forms of cancer in part because of the deadly nature of the disease, which will kill about one in six of the 47,700 people it is expected to strike this year. Unless melanoma is caught early and removed, there is no effective treatment, although research groups have been testing vaccine therapies for the disease. However, Lee worried that unless researchers better understood immune dysfunctions in those people, the vaccines would have a low probability of success. "If you don't address the underlying immune defects, then vaccines won't do any good," Lee said.
The group started by separating out the four major types of immune cells from people with melanoma and from healthy people. These cells were B cells, two types of T cells and NK, or natural killer, cells. Then, postdoctoral scholar Rebecca Critchley-Thorne, PhD, lead author of the paper, looked in the immune cells of healthy people vs. those with melanoma to see if they had the same levels of activation of roughly 20,000 genes.
She found that the B cells and both types of T cells in people with melanoma showed activity levels that differed from healthy people in only 25 of those genes. Seventeen of those 25 were normally turned on in response to interferon.
"Interferon normally acts as a critical signal in activating immune cells," said Critchley-Thorne. Without the ability to respond to interferon, those cells might detect the cancer but won't activate properly.
This type of experiment only shows that certain genes are turned on at different levels in people with melanoma. It doesn't prove that the cells behave differently than the immune cells of normal people. To verify that the interferon signaling was defective in people with melanoma, Critchley-Thorne isolated those cells and exposed them to interferon.
As predicted, immune cells from people with melanoma also failed to respond normally to the immune activation signal. However, she found that if she left the cells in the presence of a high dose of interferon for much longer than would normally be required, those cells did begin responding.
Lee said the finding explains why a common melanoma treatment, in which some doctors have treated patients with prolonged exposure to interferon, sometimes helps. "Doctors knew it worked in some people but didn't know why," Lee said. This data suggests that treatment works by overcoming the immune system's inability to react properly to interferon.
If Lee's suspicion turns out to be true, doctors may be able to screen melanoma patients for interferon response and provide prolonged interferon treatment for only those patients whose immune cells have defects in that pathway. That means patients who wouldn't benefit from the treatment could avoid suffering through interferon's flu-like side effects.
Amy Adams | EurekAlert!
GLUT5 fluorescent probe fingerprints cancer cells
20.04.2018 | Michigan Technological University
Scientists re-create brain neurons to study obesity and personalize treatment
20.04.2018 | Cedars-Sinai Medical Center
At the Hannover Messe 2018, the Bundesanstalt für Materialforschung und-prüfung (BAM) will show how, in the future, astronauts could produce their own tools or spare parts in zero gravity using 3D printing. This will reduce, weight and transport costs for space missions. Visitors can experience the innovative additive manufacturing process live at the fair.
Powder-based additive manufacturing in zero gravity is the name of the project in which a component is produced by applying metallic powder layers and then...
Physicists at the Laboratory for Attosecond Physics, which is jointly run by Ludwig-Maximilians-Universität and the Max Planck Institute of Quantum Optics, have developed a high-power laser system that generates ultrashort pulses of light covering a large share of the mid-infrared spectrum. The researchers envisage a wide range of applications for the technology – in the early diagnosis of cancer, for instance.
Molecules are the building blocks of life. Like all other organisms, we are made of them. They control our biorhythm, and they can also reflect our state of...
University of Connecticut researchers have created a biodegradable composite made of silk fibers that can be used to repair broken load-bearing bones without the complications sometimes presented by other materials.
Repairing major load-bearing bones such as those in the leg can be a long and uncomfortable process.
Study published in the journal ACS Applied Materials & Interfaces is the outcome of an international effort that included teams from Dresden and Berlin in Germany, and the US.
Scientists at the Helmholtz-Zentrum Dresden-Rossendorf (HZDR) together with colleagues from the Helmholtz-Zentrum Berlin (HZB) and the University of Virginia...
Novel highly efficient and brilliant gamma-ray source: Based on model calculations, physicists of the Max PIanck Institute for Nuclear Physics in Heidelberg propose a novel method for an efficient high-brilliance gamma-ray source. A giant collimated gamma-ray pulse is generated from the interaction of a dense ultra-relativistic electron beam with a thin solid conductor. Energetic gamma-rays are copiously produced as the electron beam splits into filaments while propagating across the conductor. The resulting gamma-ray energy and flux enable novel experiments in nuclear and fundamental physics.
The typical wavelength of light interacting with an object of the microcosm scales with the size of this object. For atoms, this ranges from visible light to...
13.04.2018 | Event News
12.04.2018 | Event News
09.04.2018 | Event News
25.04.2018 | Physics and Astronomy
25.04.2018 | Physics and Astronomy
25.04.2018 | Information Technology