Tumors in melanoma patients cause the body’s immune defense to weaken to a point where it’s not able to kill cancerous cells in the tumor, according to new research published in the Journal of Clinical Investigation.
The researchers, led by Dr Sophia Karagiannis and Professor Frank Nestle at King’s College London, UK, also found a potential antibody biomarker which could help determine what treatments are best for different people.
Previous research has indicated that antibodies are produced in melanoma patients that attack cancer cells. However, a patient’s immune response is often unable to prevent the cancer from spreading.
The most common antibody class that the body’s immune system produces is the class “IgG”. The most effective antibodies that are produced belong to the IgG1 subclass, while the least efficient belong to the IgG4 subclass.
A total of 80 different patients from the melanoma clinic of St John’s Institute of Dermatology at Guy’s and St Thomas’ NHS Foundation Trust, London, had their tumor tissue and blood analyzed.
They found that melanoma tumors attract IgG4 antibodies – the weakest immune response – and interfere with the circulating IgG1 antibodies.
Dr Karagiannis added:
“We were able to mimic the conditions created by melanoma tumours and showed that B cells can be polarised to produce IgG4 antibodies in the presence of cancer cells.”
The body’s immune response was found to be normal in the presence of healthy cells, with IgG1 antibodies as the most common.
The researchers engineered IgG1 and IgG4 antibodies against a tumor antigen. They identified that IgG4 wasn’t as efficient IgG1 in triggering immune cells to kill cancer cells. In addition, IgG4 prevented the IgG1 antibody from effectively killing tumor cells.
They also found that patients with high IgG4 levels in their blood tended to have a worse prognosis than those with normal levels of the antibody. This might mean that IgG4 could indicate disease progression.
Dr Karagiannis said:
“This work bears important implications for future therapies since not only are IgG4 antibodies ineffective in activating immune cells to kill tumours but they also work by blocking antibodies from killing tumour cells.
The latter means that 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.”
According to Professor Nestle: “Now, with the help of our NIHR Biomedical Research Centre, more work needs to be done on developing IgG4 as a potential clinical and prognostic biomarker which can improve patient care by informing clinical decisions and helping to identify patients most likely to respond to treatments.”
The findings could help drive further research into future cancer therapies. Antibodies were known as the “magic bullets” of cancer care, and according to researchers at the Georgetown Lombardi Comprehensive Cancer Center, they are fulfilling that promise, with many more advances on the way.
Written by Joseph Nordqvist