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

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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; IgG4 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.

Original languageEnglish
Pages (from-to)303-319
Number of pages17
JournalPigment Cell and Melanoma Research
Issue number3
Publication statusPublished - 25 Feb 2022


  • antibody
  • B-cell
  • cancer
  • checkpoint inhibitor response
  • IgA
  • IgD
  • IgG
  • immunoglobulin
  • melanoma
  • tertiary lymphoid structure (TLS)


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