Cancer cells use an array of different techniques to try to outrun a patient’s immune system.
But some of the latest cancer treatments attempt to disrupt these tactics, allowing the immune system to tackle the tumour.
But, your immune system is a diverse team of cells, all with different skills and attributes.
Your ‘attack’ is made up of cells like killer T cells, designed to hunt down and tackle rogue or infected cells.
But other more defensive immune cells protect your body, helping to heal wounded tissue.
New research from our scientists in Edinburgh – led by Professor Margaret Frame and published in the journal Cell – suggests that cancer cells can recruit these protective immune cells to their own team, surrounding them to keep back the immune system’s killer cells.
So how do cancer cells recruit this protective ‘huddle’ and avoid being tackled by the immune system?
No FAK no glory
Last year we wrote about a molecule called Focal Adhesion Kinase (FAK) that cancer cells produce, which helps them resist treatment.
FAK switches on a whole host of genes and signals inside cells that control various processes ranging from how sticky a cell is, to whether it moves, survives or dies. And all of these signals can help a cancer to grow and spread.
FAK has also been shown to be important in the growth and spread of prostate, bowel and breast cancers in mice. And the cells that make up some patients’ cancers’ also seem to produce excess amounts of FAK.
So the Edinburgh team wanted to know precisely which signals FAK changes in cancer cells to help them grow – and also how this was linked to the immune system.
Working with mice that had a type of skin cancer called squamous cell carcinoma, the team switched FAK production on or off within the cancer cells to see how this affected their growth.
The cancer cells that could still produce FAK were able to keep growing and growing. But without FAK, the cancer cells were unable to hold back the immune system’s killer T cells, and within three weeks they were completely destroyed.
Next, the team examined the different immune cells surrounding the tumours that still produced FAK, and discovered that many were protective, rather than the killer variety.
These protective cells, called T regulatory cells, dampen down the responses from other immune cells, like killer T cells – and they’ve been known for some time to be a key component of cancer’s strategy to keep the body’s immune response at bay.
But how did they end up swarming the tumour, and why are they only around when FAK is there?
Winning the line out
The researchers then looked at other genes switched on in the FAK-producing cancer cells. Here they found that FAK was switching on an entire network of chemical signals called chemokines.
These act as distress signals, allowing them to call for help from the immune system. And what the team discovered was that FAK ultimately triggered the production of chemokines known to recruit protective immune cells.
Similar to a Rugby maul, the cancer cells were using FAK to gather the protective T regulatory cells around them to ward off the cancer killing T cells.
So why does FAK have such an important role in cancer? The key, according to Dr Adam Byron, an author on the study and researcher at the University of Edinburgh, was finding out that when cells are stressed by becoming cancerous, FAK’s function changes.
“Under cellular stress, FAK is transported to the cell’s nucleus where it has access to its DNA. There it is able to control the production of a whole array of molecules that it would not normally influence.”
And this dual role is something that Adam was particularly surprised to see.
“Finding out that cancer cells co-opt FAK to force it to do something entirely different from its normal function took us by surprise,” he says.
So how can this knowledge help improve things for patients?
Turning it over at the try line
Fortunately, an experimental drug that targets FAK is already being developed. And the team has already started testing the drug to see if it could stop FAK’s ability to call in protective immune cells.
So far they have found that, within 24 days of treatment with the drug, the cancer cells were eradicated in the mice: a promising preliminary finding.
Crucially, the drug is already being tested in early stage clinical trials to find out the safest dose to give to people. And the results of further trials will show whether it will produce the same cancer-killing effects in patients.
But what this latest finding brings to the squad is the potential to convert the immune environment around cancer cells, and provide real hope for cancer patients.
And that’s certainly worth a try.
Alan
Reference
Serrels, A., et al. (2015). Nuclear FAK Controls Chemokine Transcription, Tregs, and Evasion of Anti-tumor Immunity Cell, 163 (1), 160-173 DOI: 10.1016/j.cell.2015.09.001
from Cancer Research UK - Science blog http://ift.tt/1NYT80F
Cancer cells use an array of different techniques to try to outrun a patient’s immune system.
But some of the latest cancer treatments attempt to disrupt these tactics, allowing the immune system to tackle the tumour.
But, your immune system is a diverse team of cells, all with different skills and attributes.
Your ‘attack’ is made up of cells like killer T cells, designed to hunt down and tackle rogue or infected cells.
But other more defensive immune cells protect your body, helping to heal wounded tissue.
New research from our scientists in Edinburgh – led by Professor Margaret Frame and published in the journal Cell – suggests that cancer cells can recruit these protective immune cells to their own team, surrounding them to keep back the immune system’s killer cells.
So how do cancer cells recruit this protective ‘huddle’ and avoid being tackled by the immune system?
No FAK no glory
Last year we wrote about a molecule called Focal Adhesion Kinase (FAK) that cancer cells produce, which helps them resist treatment.
FAK switches on a whole host of genes and signals inside cells that control various processes ranging from how sticky a cell is, to whether it moves, survives or dies. And all of these signals can help a cancer to grow and spread.
FAK has also been shown to be important in the growth and spread of prostate, bowel and breast cancers in mice. And the cells that make up some patients’ cancers’ also seem to produce excess amounts of FAK.
So the Edinburgh team wanted to know precisely which signals FAK changes in cancer cells to help them grow – and also how this was linked to the immune system.
Working with mice that had a type of skin cancer called squamous cell carcinoma, the team switched FAK production on or off within the cancer cells to see how this affected their growth.
The cancer cells that could still produce FAK were able to keep growing and growing. But without FAK, the cancer cells were unable to hold back the immune system’s killer T cells, and within three weeks they were completely destroyed.
Next, the team examined the different immune cells surrounding the tumours that still produced FAK, and discovered that many were protective, rather than the killer variety.
These protective cells, called T regulatory cells, dampen down the responses from other immune cells, like killer T cells – and they’ve been known for some time to be a key component of cancer’s strategy to keep the body’s immune response at bay.
But how did they end up swarming the tumour, and why are they only around when FAK is there?
Winning the line out
The researchers then looked at other genes switched on in the FAK-producing cancer cells. Here they found that FAK was switching on an entire network of chemical signals called chemokines.
These act as distress signals, allowing them to call for help from the immune system. And what the team discovered was that FAK ultimately triggered the production of chemokines known to recruit protective immune cells.
Similar to a Rugby maul, the cancer cells were using FAK to gather the protective T regulatory cells around them to ward off the cancer killing T cells.
So why does FAK have such an important role in cancer? The key, according to Dr Adam Byron, an author on the study and researcher at the University of Edinburgh, was finding out that when cells are stressed by becoming cancerous, FAK’s function changes.
“Under cellular stress, FAK is transported to the cell’s nucleus where it has access to its DNA. There it is able to control the production of a whole array of molecules that it would not normally influence.”
And this dual role is something that Adam was particularly surprised to see.
“Finding out that cancer cells co-opt FAK to force it to do something entirely different from its normal function took us by surprise,” he says.
So how can this knowledge help improve things for patients?
Turning it over at the try line
Fortunately, an experimental drug that targets FAK is already being developed. And the team has already started testing the drug to see if it could stop FAK’s ability to call in protective immune cells.
So far they have found that, within 24 days of treatment with the drug, the cancer cells were eradicated in the mice: a promising preliminary finding.
Crucially, the drug is already being tested in early stage clinical trials to find out the safest dose to give to people. And the results of further trials will show whether it will produce the same cancer-killing effects in patients.
But what this latest finding brings to the squad is the potential to convert the immune environment around cancer cells, and provide real hope for cancer patients.
And that’s certainly worth a try.
Alan
Reference
Serrels, A., et al. (2015). Nuclear FAK Controls Chemokine Transcription, Tregs, and Evasion of Anti-tumor Immunity Cell, 163 (1), 160-173 DOI: 10.1016/j.cell.2015.09.001
from Cancer Research UK - Science blog http://ift.tt/1NYT80F
Aucun commentaire:
Enregistrer un commentaire