November 04, 2010
Tumor Protein Suppresses Immune Attack On Cancer
Stromal cells in tumors excrete a protein that tells the immune system not to attack cancer cells. A way to suppress that protein would open up tumors to immune attack.
Researchers at the University of Cambridge hope to revolutionise cancer therapy after discovering one of the reasons why many previous attempts to harness the immune system to treat cancerous tumours have failed.
New research, published today in the journal Science, reveals that a type of stromal cell found in many cancers which expresses fibroblast activation protein alpha (FAP), plays a major role in suppressing the immune response in cancerous tumours – thereby restricting the use of vaccines and other therapies which rely on the body's immune system to work. They have also found that if they destroy these cells in a tumour immune suppression is relieved, allowing the immune system to control the previously uncontrolled tumour.
Tumors need many mutations in order to grow. Mutations that allow them to suppress immune response probably are among the mutations that make cancers more deadly.
In transgenic mice wiping out the stromal cells that make FAP opened up the tumors to immune attack.
In order to determine if FAP expressing stromal cells contribute to the resistance of a tumour to vaccination, the researchers created a transgenic mouse model which allowed them to destroy cells which expressed FAP. When FAP-expressing cells were destroyed in tumours in mice with established Lewis lung carcinomas (of which only 2% of the tumour cells are FAP-expressing), the cancer began to rapidly 'die'. The Fearon lab now hopes to collaborate with scientists at the CRUK Cambridge Research Institute to evaluate the effects of depleting FAP-expressing cells in a mouse model that more closely resemble human cancer, and to examine FAP-expressing cells of human tumours.
Drugs that would suppress or block FAP might work to activate the immune system to wipe out cancers. During such a drug treatment the patient might also experience harm from auto-immune attacks on healthy cells. Well, as compared to death from terminal cancer a temporary auto-immune disease would probably be the lesser of two evils.
"Well, as compared to death from terminal cancer a temporary auto-immune disease would probably be the lesser of two evils."
You sure called that one.
Back to the original findings, I wonder how many other people notice an increase in size and number of skin growths (warts, moles, etc) when a tumor forms?
Gotta keep those stromal cells from FAPping..
Ah yes, another sure cure just on the horizon. Read this article carefully, it will be the last time you see it.
VEGF inhibitors (I was treated with Sutent)are similar drugs. They interfere with a protein that encourages angiogenesis (development of new blood vessels to supply a tumor with blood needed for growth). I have had a extraordinary response to treatment. Three years ago, when diagnosed with Renal Clear Cell cancer, I had too many lung mets to count (two largest the size of golf balls). I had large bone mets as well (largest about 2 inches). While the bone is not completely regrown, all my mets have shrunk essentially to nothing and I have no active disease by PET scan. Other drugs (MDX 1106 and 1105), currently in clinic trials, are similar to this drug in that they prevent the tumor from tricking the immune system into ignoring the cancer cells. We are just at the beginning of targeted therapies for cancer. Not all cancers will be treatable soon and not all patients will benefit. However, these advances are moving cancer therapy ahead in leaps and bounds. If we can maintain a medical system that encourages innovation and new treatment development, cancer treatments will improve dramatically in the near future. Cancer is becoming a chronic disease for many patients because of this type of treatment. Hopefully, we can continue the progress.
Yes, absolutely, cancer evolves. In fact, cancer is not genetically homogeneous. The more successful mutations outcompete genetic versions that do not have as many of the mutations that boost its spread. Cancer evolves to:
- secrete angiogenesis factors.
- secrete immune suppression factors.
- to survive in the bloodstream to spread wider.
- to lose dependence on hormones for growth (e.g. prostate cancers that mutate to cease needing testosterone to grow).
- to break down and become less sensitive to chemo therapy and other drugs used against it.
- replicate more rapidly.
- change in other ways that help in its growth and spread.