Melanoma tumors create conditions that attract immunoglobulin G4 (IgG4), which is the least effective B-cell antibody class in terms of activating immune system response and also keeps at bay other IgG cells more capable of destroying the tumor cells.

As prior research by some of the current investigators demonstrated, persons with melanoma do produce antibodies that attack tumor cells, yet the patient’s immune system is often ineffective at preventing the cancer from progressing. In the new analysis, a team led by Dr. Sophia N. Karagiannis and Prof. Frank Nestle, both of King’s College London in London, England, sought to explain the presence and functional implications of IgG4 in malignant melanoma.

When the investigators simulated the conditions created by melanoma tumors, they learned that B cells can be polarized to produce IgG4 antibodies in the presence of cancer cells, as they reported in The Journal of Clinical Investigation. Antibodies of the IgG4 subclass are thought to be the least efficient of the five classes of B-cell antibodies at activating immune cells, whereas IgG1 antibodies are the most efficient. However, the analysis revealed that IgG4 blocked the tumor-destroying actions of IgG1.

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In addition, samples from 33 persons with melanoma indicated that patients with higher blood levels of IgG4 were more likely to have a less favorable prognosis compared with patients whose IgG4 levels were closer to normal. This suggests that IgG4 could be an antibody biomarker for predicting prognosis and could identify which persons with melanoma are most likely to respond to specific treatments.