A B‐cell or a key player? The different roles of B‐cells and antibodies in melanoma

The B‐cell system plays an important role in the melanoma immune response; however, consensus has yet to be reached in many facets. Here, we comprehensively review human studies only, due to fundamental differences in the humoral response with animal models. Tumour‐infiltrating B‐cells are associated with contradictory prognostic values, reflecting a lack of agreement between studies on cell subset classification and differences in the markers used, particularly the common use of a single marker not differentiating multiple subsets. Tertiary lymphoid structures (TLS) organise T‐cells and B‐cells within tumours to generate a local anti‐tumour response and TLS presence associates with improved survival in response to immune checkpoint blockade, in late‐stage disease. Autoantibody production is increased in melanoma patients and has been proposed as biomarkers for diagnosis, prognosis and treatment/toxicity response; however, no consistent targets are yet identified. The function of antibodies in an anti‐tumour response is determined by its isotype and subclass; IgG(4) is immune‐suppressive and robustly correlate with poor patient survival in melanoma. We conclude that the current B‐cell literature needs careful interpretation based on the methods used and that we need a consensus of markers to define B‐cells and associated lymphoid organs. Furthermore, future studies need to not only examine antibody targets, but also isotypes when considering functional roles.