Analysis of tumour and blood samples shows that melanoma knocks out the body's best immune defence.
A potential test could work out which patients are likely to respond to treatment, the Journal of Clinical Investigation reports.
Cancer Research UK said the body's response was a "complex puzzle".
Previous work from the team at King's College London showed that while patients with melanoma produced antibodies that could attack tumour cells, the immune system often seemed powerless to stop the cancer progressing.
But in the latest research they discovered that the subtype of antibody attracted by the melanoma cells was the most ineffective at mounting the right sort of response.
In samples from 80 melanoma patients they say that the conditions created by the tumour attract IgG4 antibodies, which mount the weakest response and in turn interfere with any "strong" IgG1 antibodies that might be present.