Although we report the presence of anti-tumor antibodies produced by patient memory B cells, and these cells were stimulated ex vivo to secrete antibodies, it is not clear whether tumor antigen-reactive B cells are activated in patients to secrete antibodies or whether these humoral responses are capable of exerting any beneficial anti-tumoral activities in the same patients in vivo. In the 21 patient cohort at different disease stages in this study, we were not able to draw any conclusions regarding the relationship between tumor cell reactivity and clinical disease progression in the short term (6 months to 2 year follow up) or associations with any particular disease treatment regimes. However, monitoring mature memory B cells and their antibody repertoires together with clinical outcomes in patients over a long period of time may help identify any correlations between melanoma-reactive mature memory B cell responses and disease progression. Additionally, future studies may help identify particular components of the humoral response which may hold clinical relevance, and elucidate the potential merits of monitoring these responses in relation to therapies, or of evaluating humoral responses as a prognostic factor to clinical outcomes.