Nav: Home

What protects killer immune cells from harming themselves?

November 27, 2019

White blood cells, which release a toxic potion of proteins to kill cancerous and virus-infected cells, are protected from any harm by the physical properties of their cell envelopes, find scientists from UCL and the Peter MacCallum Cancer Centre in Melbourne.

Until now, it has been a mystery to scientists how these white blood cells - called cytotoxic lymphocytes - avoid being killed by their own actions and the discovery could help explain why some tumours are more resistant than others to recently developed cancer immunotherapies.

The research, published in Nature Communications, highlights the role of the physical properties of the white blood cell envelope, namely the molecular order and electric charge, in providing such protection.

According to Professor Bart Hoogenboom (London Centre for Nanotechnology, UCL Physics & Astronomy and UCL Structural & Molecular Biology), co-author of the study: "Cytotoxic lymphocytes, or white blood cells, rid the body of disease by punching holes in rogue cells and by injecting poisonous enzymes inside. Remarkably, they can do this many times in a row, without harming themselves. We now know what effectively prevents these white blood cells from committing suicide every time they kill one of their targets."

The scientists made the discovery by studying perforin, which is the protein responsible for the hole-punching. They found that perforin's attachment to the cell surface strongly depends on the order and packing of the molecules - so-called lipids - in the membrane that surrounds and protects the white blood cells.

More order and tighter packing of the lipid molecules led to less perforin binding, and when they artificially disrupted the order of this lipid in the white blood cells, the cells became more sensitive to perforin.

However, they also found that when the white blood cells were exposed to so much perforin that some of it stuck to their surface, the bound perforin still failed to kill the white blood cells, indicating that there must be another layer of protection. This turned out to be the negative charge of some lipid molecules sent to the cell surface, which bound the remaining perforin and blocked it from damaging the cell.

Joint first author, Dr Adrian Hodel, who screened and studied many membrane systems for this work, said: "We have long known that local lipid order can change how cells communicate which each other, but it was rather surprising that the precise physical membrane properties can also provide such an important layer of protection against molecular hole-punchers."

In Melbourne, joint first author Jesse Rudd-Schmidt, who focused on the characterisation of the white blood cells in Associate-Professor Ilia Voskoboinik's laboratory, said: "What we have found helps to explain how our immune system can be so effective in killing rogue cells. We are now also keen to investigate if cancer cells may use similar protection to avoid being killed by immune cells, which would then explain some of the large variability in patient response to cancer immunotherapies."
-end-
The work was kindly funded by the Australian National Health and Medical Research Council and by the UK Biotechnology and Biological Sciences Research Council and Engineering and Physical Sciences Research Council, and by the Sackler Foundation.

University College London

Related Immune Cells Articles:

How tumor cells evade the immune defense
Scientists are increasingly trying to use the body's own immune system to fight cancer.
How immune cells activate the killer mode
Freiburg researchers find missing link in immune response.
Breast cancer cells can reprogram immune cells to assist in metastasis
Johns Hopkins Kimmel Cancer Center investigators report they have uncovered a new mechanism by which invasive breast cancer cells evade the immune system to metastasize, or spread, to other areas of the body.
Breast cancer cells turn killer immune cells into allies
Researchers at Johns Hopkins University School of Medicine have discovered that breast cancer cells can alter the function of immune cells known as Natural killer (NK) cells so that instead of killing the cancer cells, they facilitate their spread to other parts of the body.
Engineered immune cells recognize, attack human and mouse solid-tumor cancer cells
CAR-T therapy has been used successfully in patients with blood cancers such as lymphoma and leukemia.
Mapping immune cells in brain tumors
It is not always possible to completely remove malignant brain tumors by surgery so that further treatment is necessary.
Nutrient deficiency in tumor cells attracts cells that suppress the immune system
A study led by IDIBELL researchers and published this week in the American journal PNAS shows that, by depriving tumor cells of glucose, they release a large number of signaling molecules.
Experience matters for immune cells
The discovery that immune T cells have a spectrum of responsiveness could shed light on how our immune system responds to infections and cancer, and what goes wrong in immune diseases.
Immune cells against Alzheimer's?
German researchers have developed a novel, experimental approach against Alzheimer's.
Arming the body's immune cells
Researchers at UC have discovered a previously unknown mechanism that could explain the reason behind decreased immune function in cancer patients and could be a new therapeutic target for immunotherapy for those with head and neck cancers.
More Immune Cells News and Immune Cells Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Debbie Millman: Designing Our Lives
From prehistoric cave art to today's social media feeds, to design is to be human. This hour, designer Debbie Millman guides us through a world made and remade–and helps us design our own paths.
Now Playing: Science for the People

#574 State of the Heart
This week we focus on heart disease, heart failure, what blood pressure is and why it's bad when it's high. Host Rachelle Saunders talks with physician, clinical researcher, and writer Haider Warraich about his book "State of the Heart: Exploring the History, Science, and Future of Cardiac Disease" and the ails of our hearts.
Now Playing: Radiolab

Insomnia Line
Coronasomnia is a not-so-surprising side-effect of the global pandemic. More and more of us are having trouble falling asleep. We wanted to find a way to get inside that nighttime world, to see why people are awake and what they are thinking about. So what'd Radiolab decide to do?  Open up the phone lines and talk to you. We created an insomnia hotline and on this week's experimental episode, we stayed up all night, taking hundreds of calls, spilling secrets, and at long last, watching the sunrise peek through.   This episode was produced by Lulu Miller with Rachael Cusick, Tracie Hunte, Tobin Low, Sarah Qari, Molly Webster, Pat Walters, Shima Oliaee, and Jonny Moens. Want more Radiolab in your life? Sign up for our newsletter! We share our latest favorites: articles, tv shows, funny Youtube videos, chocolate chip cookie recipes, and more. Support Radiolab by becoming a member today at Radiolab.org/donate.