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article imageMelanoma 'shuts down' body's premier immune defence

By Greta McClain     Mar 4, 2013 in Science
London - A new study by UK researchers shows a deadly form of skin cancer is capable of basically shutting down the body's strongest immune response.
King's College London researchers found that melanoma, the most dangerous form of skin cancer, shuts down the body's immune system by intentionally creating conditions that weaken the body's most potent B cells immune response, while attracting the least effective.
The body's B cells secrete substances called antibodies which attack antigens in the bloodstream. There are four types of antibodies, with IgG1 being the most effective at activating immune cells, while IgG4 is believed to be the least effective.
The researchers, led by Dr Sophia Karagiannis and Professor Frank Nestle, took tumor and blood samples from 80 melanoma patients. By recreating the conditions found in the body when melanoma cells are present, they found that IgG4 responded to the cancerous cells while also hampering the circulation of IgG1, essentially "shutting down" the immune response. Karagiannis told News Medical:
"We were able to mimic the conditions created by melanoma tumors and showed that B cells can be polarized to produce IgG4 antibodies in the presence of cancer cells. This work bears important implications for future therapies since not only are IgG4 antibodies ineffective in activating immune cells to kill tumors but they also work by blocking [IgG1] antibodies from killing tumor cells."
By also testing samples from 33 patients, the study found that patients who had an increased level of IgG4 in their blood typically had a poorer prognosis than patients with levels in the normal range.
Researchers believe they can use this latest information to develop new cancer treatment therapies by possibly explaining why some immune boosting treatments are less effective in certain patients, with Karagiannis saying:
"IgG4 not only prevents the patient's more powerful antibodies from eradicating cancer, but could also explain why treatments may be hindered by those native IgG4 antibodies found in patients, making therapeutic antibodies less effective."
They are also hopeful the research can also lead to a potential test which identify patients most likely to respond to treatments. Nestle told the BBC:
"This study can also inform the rational design of novel strategies to counteract IgG4 actions."
More about Cancer, Skin cancer, Melanoma, Immune System, Immune
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