Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Scientists link common immune cell to failure of checkpoint inhibitors in lung cancer

20.12.2019

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


Microscope image of a lung cancer sample from a patient who did not respond to checkpoint inhibitors. The T cells (in blue) are trapped whereas the neutrophils (in purple) are widespread throughout the cancer cells (white/gray).

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.

Media Contact

Molly McElroy
mwmcelro@fredhutch.org
206-667-6651

 @FredHutch

http://www.fredhutch.org 

Molly McElroy | EurekAlert!
Further information:
https://www.fredhutch.org/en/news/center-news/2019/12/lung-cancer-checkpoint-inhibitors-neutrophils.html
http://dx.doi.org/10.1172/jci.insight.130850

More articles from Life Sciences:

nachricht First SARS-CoV-2 genomes in Austria openly available
03.04.2020 | CeMM Forschungszentrum für Molekulare Medizin der Österreichischen Akademie der Wissenschaften

nachricht Do urban fish exhibit impaired sleep? Light pollution suppresses melatonin production in European perch
03.04.2020 | Leibniz-Institut für Gewässerökologie und Binnenfischerei (IGB)

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Harnessing the rain for hydrovoltaics

Drops of water falling on or sliding over surfaces may leave behind traces of electrical charge, causing the drops to charge themselves. Scientists at the Max Planck Institute for Polymer Research (MPI-P) in Mainz have now begun a detailed investigation into this phenomenon that accompanies us in every-day life. They developed a method to quantify the charge generation and additionally created a theoretical model to aid understanding. According to the scientists, the observed effect could be a source of generated power and an important building block for understanding frictional electricity.

Water drops sliding over non-conducting surfaces can be found everywhere in our lives: From the dripping of a coffee machine, to a rinse in the shower, to an...

Im Focus: A sensational discovery: Traces of rainforests in West Antarctica

90 million-year-old forest soil provides unexpected evidence for exceptionally warm climate near the South Pole in the Cretaceous

An international team of researchers led by geoscientists from the Alfred Wegener Institute, Helmholtz Centre for Polar and Marine Research (AWI) have now...

Im Focus: Blocking the Iron Transport Could Stop Tuberculosis

The bacteria that cause tuberculosis need iron to survive. Researchers at the University of Zurich have now solved the first detailed structure of the transport protein responsible for the iron supply. When the iron transport into the bacteria is inhibited, the pathogen can no longer grow. This opens novel ways to develop targeted tuberculosis drugs.

One of the most devastating pathogens that lives inside human cells is Mycobacterium tuberculosis, the bacillus that causes tuberculosis. According to the...

Im Focus: Physicist from Hannover Develops New Photon Source for Tap-proof Communication

An international team with the participation of Prof. Dr. Michael Kues from the Cluster of Excellence PhoenixD at Leibniz University Hannover has developed a new method for generating quantum-entangled photons in a spectral range of light that was previously inaccessible. The discovery can make the encryption of satellite-based communications much more secure in the future.

A 15-member research team from the UK, Germany and Japan has developed a new method for generating and detecting quantum-entangled photons at a wavelength of...

Im Focus: Junior scientists at the University of Rostock invent a funnel for light

Together with their colleagues from the University of Würzburg, physicists from the group of Professor Alexander Szameit at the University of Rostock have devised a “funnel” for photons. Their discovery was recently published in the renowned journal Science and holds great promise for novel ultra-sensitive detectors as well as innovative applications in telecommunications and information processing.

The quantum-optical properties of light and its interaction with matter has fascinated the Rostock professor Alexander Szameit since College.

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

13th AKL – International Laser Technology Congress: May 4–6, 2022 in Aachen – Laser Technology Live already this year!

02.04.2020 | Event News

“4th Hybrid Materials and Structures 2020” takes place over the internet

26.03.2020 | Event News

Most significant international Learning Analytics conference will take place – fully online

23.03.2020 | Event News

 
Latest News

Capturing 3D microstructures in real time

03.04.2020 | Materials Sciences

First SARS-CoV-2 genomes in Austria openly available

03.04.2020 | Life Sciences

Do urban fish exhibit impaired sleep? Light pollution suppresses melatonin production in European perch

03.04.2020 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>