Biosingularity

Newly discovered killer cell fights cancer

Posted on: March 6, 2006

A mouse immune cell that plays dual roles as both assassin and messenger, normally the job of two separate cells, has been discovered by an international team of researchers. The discovery has triggered a race among scientists to find a human equivalent of the multitasking cell, which could one day be a target for therapies that seek out and destroy cancer.

“In the same way that intelligence and law enforcement agencies can face deadly threats together instead of separately, this one cell combines the ability to kill foreign pathogens and distribute information about that experience,” says Drew Pardoll, M.D., Ph.D., the Seraph Professor of Oncology at the Johns Hopkins Kimmel Cancer Center.

“We think this hybrid cell speeds up immune reactions and makes the system more efficient,” adds Pardoll, whose findings are reported in the February issue of Nature Medicine.

The Hopkins investigators speculate that the hybrid, dubbed “IKDC” for interferon-producing killer dendritic cell, has been missed by cancer biologists because it is rare, making up one-tenth of cells in the spleen with similar features, such as other dendritic cells, according to Frank Housseau, Ph.D., research associate at Hopkins’ Kimmel Cancer Center and member of Pardoll’s immunology laboratory.

Most of the immune system typically works through a web of cross-talk and signaling among a variety of cells. One of the first immune cells that invading bacteria or cancer cells – both of which carry antigens that alert the immune system – may encounter is a natural killer (NK) cell. As its name implies, NK cells deliver a deadly blow by poking holes in the invader’s outer membrane. Then, NK cells secrete molecules that reach other immune cells, including dendritic cells, known as the main messenger for the immune system. Dendritic cells spread “look here” information about foreign invaders to other immune cells, but do not actually kill the invaders.

It was while investigating a particular type of dendritic cell that Housseau noticed the outer membranes of these cells were studded with what were supposed to be hallmarks of NK cells, akin to finding feathers on a dog.

“We thought we were looking at dendritic cells, but we were wrong – they were some type of NK-dendritic cell blend,” says Housseau. The blended cell turned out to be a newly identified actor on the immune system stage that retains all the molecular characteristics of both NK and dendritic cells.

Probing further, Housseau scoured the surface of IKDCs to create a sketch of its molecular profile. He found that it produces both types of interferon proteins, normally secreted independently by NK and dendritic cells. He also found both NK and dendriticlike molecules on the surface of IKDCs. Housseau calculated that they account for about 10 percent of conventional dendritic cells in the spleen.

IKDCs begin their lives behaving like an NK cell. After the cell encounters a pathogen, the cell switches roles from killer to dendriticlike messenger, and, according to the researchers, the swap occurs only once. Then, the cell dies and is replenished by the bone marrow.

“When an IKDC cell switches to its messenger function, the transformation is quite astonishing,” says Pardoll. The cell sprouts long, hairy tentacles called dendrites. It uses its “arms” to increase the amount of surface area it reaches to communicate and interact with other immune cells.

In the next step of their investigation, the scientists tracked the location of fluorescent-tagged IKDCs and their corresponding stage of transformation after infecting mice with bacteria called listeria. In assassin-mode, the IKDCs were found in the blood, lining of the gut, liver and other organs – all areas where there is close contact with environmental pathogens. “Here, IKDCs are ready to sense invaders and spring into action,” says Housseau.

Then, the group tracked the cells to the main messenger center of the immune system – the lymph nodes. Here, they found approximately 35 percent of the original group of IKDCs now secreting communication molecules signaling a switch to messenger-mode.

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Simultaneously, Housseau’s colleagues in France, led by Laurence Zitvogel at the Institut Gustave Roussy, tested whether IKDCs are culprits in killing cancer by injecting mice with a cancer drug called Gleevec, which blocks an abnormal protein produced by cancer cells, and a growth factor for NK cells. The drug-growth factor combo served as a lure, leading the IKDCs to tumors implanted in the mice. The results were that tumors shrunk in mice, which received injections of IKDCs, but not in those receiving conventional NK cells only. Evidence from the shrunken tumors revealed certain “cell-killing” proteins that could be traced to IKDCs. These results are published separately in Nature Medicine.

Housseau’s group is conducting further studies to verify the role of IKDC cells in infection and cancer. Meanwhile, the group is profiling IKDC genes to find a specific marker that could help them identify a human counterpart.

Link to abstracts of the papers:
Abstract 1 from pubmed

abstract 2 from Nature MedicineSource: Johns Hopkins Medical Institution

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26 Responses to "Newly discovered killer cell fights cancer"

[...] A mouse immune cell that plays dual roles as both assassin and messenger, normally the job of two separate cells, has been discovered by an international team of researchers. The discovery has triggered a race among scientists to find a human equivalent of the multitasking cell, which could one day be a target for therapies that seek out and destroy cancer. [...]

Amazing… This is excellent news.

[...] Read the article and see what you think. http://biosingularity.wordpress.com/2006/03/06/newly-discovered-killer-cell-fights-cancer/ No Comments so far Leave a comment RSS feed for comments on this post. TrackBack URI Leave a comment Line and paragraph breaks automatic, e-mail address never displayed, HTML allowed: <a href="" title=""> <abbr title=""> <acronym title=""> <b> <blockquote cite=""> <code> <em> <i> <strike> <strong> [...]

This is of particular interest to me and I would hope, my grandfather. He is currently troubled with several small malignant tumors. It is my understanding that not a single one of these tumors are doing direct harm, but that they will gradually distribute themselves throughout his body until one of the new tumors starts causing serious health conciqunces. Doctor’s have given him only a couple months to live. Information like this makes me wish that the US FDA wasn’t such a stick in the mud, and that American Lawyer’s had some idea of what it means to innovate. One of the other posters on Digg.com mentioned that this will probably take 10 years for this to make its way into the market place and I would probably agree, but I can still wish that it somehow could make it to my Grandfather within weeks!

your grandfather could get in on the research they are doing right now to see if it helps him. be careful though because some experimental procedures are more risky than the disease itself.

I know this all sounds very promising, but you need to be aware that if you go to see this actual abstract, it is a letter to the editors of Nature Medicine. There is nothing bad about that, but it is the weakest type of publication there is in science. That isn’t to say that nothing will come of it, something might. They publish these letters to encourage people to fund and look into this new area that they are exploring. But that means that they are still probably years from making this even an experimental model in humans.

Mandy, actually most of publications in Nature and Nature Medicine are called Letters. These are still full papers. These journals publish one or two bigger articles that are not small enough to fit into 4 pages.

In contrast to what you wrote, these are the highest possible papers you can publish in biology. Nature Medicine has the highest citation impact among all biology journals. I like to remind you that Watson and Crick published their discovery of DNA structure as letter in Nature in 1953.

Also there is a second paper in the same issue of Nature Medicine, which I forgot to link above: (linked now)
http://www.nature.com.proxy.library.vanderbilt.edu/nm/journal/v12/n2/abs/nm1356.html

Both of these discoveries are extremely exciting, but we now have to find the human equivalent of these cells.

[...] Spleen cell in mice that speeds up immune system response and ultimately kills cancer. (via) [...]

he has been told that he has less than 2 months to live

amazing! thanks for the good news, you should make a digg post if you havn’t already

This is some great stuff. I’m just wondering if it’s always been there or if it was evolved? Either way it’s great!

[...] Biosingularity » Blog Archive » Newly discovered killer cell fights cancer A mouse immune cell that plays dual roles as both assassin and messenger, normally the job of two separate cells, has been discovered by an international team of researchers. The discovery has triggered a race among scientists to find a human equivalent of the multitasking cell, which could one day be a target for therapies that seek out and destroy cancer. [...]

[...] A mouse immune cell that plays dual roles as both assassin and messenger, normally the job of two separate cells, has been discovered by an international team of researchers.read more | digg story [...]

…it’s great that some people discovered this kind of discovery. we should be thankful enough with this great news….

[...] A mouse immune cell that plays dual roles as both assassin and messenger, normally the job of two separate cells, has been discovered by an international team of researchers.read more | digg story [...]

Hi, this is an urgent message: My mum has cancer and her situation is getting worse. I am searching for any kind of alternative cancer treatments. Who knows more about the discovery of killer cells? Is it possible to participate in medical experiments? I am thankful for any respond!

Hi,
I found your blog via google by accident and have to admit that youve a really interesting blog :-)
Just saved your feed in my reader, have a nice day :)

Interesting comments.. :D

Fishing Lure

I Googled for something completely different, but found your pageand have to say thanks. nice read.

[...] 8th, 2006 at 4:43 pm (Tips and Tricks) Biosingularity » Blog Archive » Newly discovered killer cell fights cancer: “A mouse immune cell that plays dual roles as both assassin and messenger, normally the job [...]

Thanks for such an informative post about cancer.I need this info because my friends mother is suffering from Colon Cancer, information mention in this article will greatly help me in offering her some advice
thank you

This is a very informative post about cancer.My niece is suffering from Liver Cancer she had after suffering from Stomach cancer.Thanks for such a useful post about cancer.
Thanks for your time to wrote this post.

I really like what you had to say here! It’s about time! Would you mind if I placed a link

back from my blog? :D

… smile

[...] Scientists discover a new “assassin” immune cell tha&#1… [...]

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I know this all sounds very promising, but you need to be aware that if you go to see this actual abstract, it is a letter to the editors of Nature Medicine. There is nothing bad about that, but it is the weakest type of publication there is in science. That isn’t to say that nothing will come of it, something might. They publish these letters to encourage people to fund and look into this new area that they are exploring. But that means that they are still probably years from making this even an experimental model in humans.

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