The study published in JCI Insight suggests how to better predict which patients will respond to immunotherapy
For many lung cancer patients, the best treatment options involve checkpoint inhibitors. These drugs unleash a patient's immune system against their disease and can yield dramatic results, even in advanced cancers.
Microscope image of a lung cancer tumor of a patient who responded to checkpoint inhibitors. T cells (in blue) were able to mount an anti-cancer response, and neutrophils (in purple) are not widespread in the tumor.
Credit: Fred Hutchinson Cancer Research Center
But checkpoint inhibitors come with a huge caveat: They only help a small subset of patients. Doctors struggle to predict who these patients are and -- just as important -- who they aren't.
Results from a new study published Dec. 19 in the journal JCI Insight could help improve those forecasts.
After analyzing tumor samples from 28 patients with non-small cell lung cancer, researchers linked a common immune cell with treatment failure. The culprit: neutrophils, the most abundant type of white blood cell.
The paper shows that the balance between neutrophils and another type of immune cell -- disease-fighting T cells -- could accurately predict which patients would respond or not. If more neutrophils than T cells were crowded into a tumor, the drugs did not curb the patients' cancers. But if the balance was reversed, checkpoint inhibitors revved up patients' immune systems against their disease.
"The study is the first to implicate neutrophils in the failure of checkpoint inhibitors," said senior author Dr. McGarry Houghton, a lung cancer immunologist at Fred Hutchinson Cancer Research Center. "Our findings also hint at a way to help patients who have this cellular signature."
In a mouse model of NSCLC, the researchers administered a drug that decreased the number of neutrophils in and around tumors. That in turn boosted the efficacy of checkpoint inhibitors -- T cells now had a clear path to attack diseased cells in the mice. The researchers now want to test this approach in NSCLC patients through a clinical trial.
"As the immunotherapy field has evolved, the main question has become: Can you identify people who will respond to these treatments?" Houghton said. "But here we're really interested in identifying the 80% of people who don't respond and finding new ways to help them."
Neutrophils are the most common white blood cell in the human body, which churns out billions of them a day. They play a vital role in the immune system, serving as first responders after infection or injury.
Early cancer researchers didn't think they played a role in the disease, Houghton said. "Cancer is a chronic disease, so people didn't think they would be very important because they don't live very long. How could they influence cancer if they're only living a few hours?"
Today, researchers know that some neutrophils can suppress the activity of T cells. And even if individual neutrophils are short-lived, collectively they can secrete chemical messages over a long timeframe. While the new paper doesn't explore precisely how neutrophils are interfering with the checkpoint inhibitors, Houghton said, the link is clear.
"This ratio of neutrophils and T cells accurately tells you who's going to respond or not," he said. "As far as we know, this is the first time anybody has shown neutrophils contribute to (checkpoint inhibitor) treatment failure."
The researchers hope that knowledge could translate to better outcomes in patients. Houghton plans to launch a clinical trial combining the neutrophil-blocking drug with checkpoint inhibitors as part of the Fred Hutch Lung Specialized Project of Research Excellence.
And they will continue to search for markers that can predict whether immunotherapy is likely to help a given patient. Being able to sort patients by their cellular signature could help doctors pick the right treatment and avoid toxicities in people unlikely to benefit from the drug, Houghton said.
"This idea of personalized immunotherapy isn't here yet," Houghton said. "But knowing which of these subtypes a patient falls into would, in the future, allow for more targeted studies and treatments. We're trying to take steps in that direction."
This work was supported by grants from the National Institutes of Health (R01CA223191 and P50CA228944) and the Seattle Translational Tumor Research program.
Molly McElroy | EurekAlert!
A new 'cool' blue
17.01.2020 | American Chemical Society
Neuromuscular organoid: It’s contracting!
17.01.2020 | Max-Delbrück-Centrum für Molekulare Medizin in der Helmholtz-Gemeinschaft
Styrofoam or copper - both materials have very different properties with regard to their ability to conduct heat. Scientists at the Max Planck Institute for Polymer Research (MPI-P) in Mainz and the University of Bayreuth have now jointly developed and characterized a novel, extremely thin and transparent material that has different thermal conduction properties depending on the direction. While it can conduct heat extremely well in one direction, it shows good thermal insulation in the other direction.
Thermal insulation and thermal conduction play a crucial role in our everyday lives - from computer processors, where it is important to dissipate heat as...
In order to advance the transfer of research developments from the field of quantum sensor technology into industrial applications, an application laboratory is being established at Fraunhofer IAF. This will enable interested companies and especially regional SMEs and start-ups to evaluate the innovation potential of quantum sensors for their specific requirements. Both the state of Baden-Württemberg and the Fraunhofer-Gesellschaft are supporting the four-year project with one million euros each.
The application laboratory is being set up as part of the Fraunhofer lighthouse project »QMag«, short for quantum magnetometry. In this project, researchers...
Microtubules, filamentous structures within the cell, are required for many important processes, including cell division and intracellular transport. A...
Researchers from the University Hospital Zurich, ETH Zurich, Wyss Zurich and the University of Zurich have developed a machine that repairs injured human livers and keep them alive outside the body for one week. This breakthrough may increase the number of available organs for transplantation saving many lives of patients with severe liver diseases or cancer.
Until now, livers could be stored safely outside the body for only a few hours. With the novel perfusion technology, livers - and even injured livers - can now...
A balloon-borne scientific instrument designed to study the origin of cosmic rays is taking its second turn high above the continent of Antarctica three and a half weeks after its launch.
SuperTIGER (Super Trans-Iron Galactic Element Recorder) is designed to measure the rare, heavy elements in cosmic rays that hold clues about their origins...
16.01.2020 | Event News
15.01.2020 | Event News
07.01.2020 | Event News
17.01.2020 | Life Sciences
17.01.2020 | Power and Electrical Engineering
17.01.2020 | Life Sciences