Abstract Background and objective The clinical significance of B-cells and their expressed antibodies is increasingly appreciated in melanoma, a highly-immunogenic tumour, for which immune checkpoint inhibitor (ICI) immunotherapy is standard care for advanced disease. We present the first scoping review reported using PRISMA-ScR (Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews) reporting guidelines in which we evaluate the phenotypes and roles of B-cells and antibodies in patients with melanoma, and their prognostic and predictive value. Methods We conducted literature searches for full-text studies in English from 1st January 2000 to 9th October 2024 using three search engines. Three reviewers conducted title and abstract screening, followed by full-text paper assessment by two independent reviewers. This study was registered with PROSPERO (CRD42024592965). Results Of 4,667 identified studies (PubMed: 827; Scopus, 2,759; OVID Medline, 1,081), 1,923 were duplicates. The remaining 3,008 were screened on title and abstract to yield 251 full-text papers, resulting in inclusion of 80 studies. Our search identified increased naive, alternatively-activated and regulatory B-cells in blood, and a bias towards differentiated and class-switched B-cell infiltrates in tumours. Consistent associations were found between B-cell density in tumours, particularly abundance of memory B-cells, and more favourable survival outcomes. Despite tumour and immune response heterogeneity, collectively, enriched B-cell signatures such as B-cell abundance, B-cell receptor (BCR) diversity and Ig gene rearrangement in tumours correlate with better ICI response. Antibody dysregulation favouring the anti-inflammatory IgG4 isotype associate with less-favourable outcomes, whilst class-switching to immune-stimulating isotypes such as IgG1 correlate with better clinical outcomes and ICI response. Antibody reactivity and autoantibody analysis revealed distinct isotype signatures in patients, the presence of cancer antigen-reactive antibodies and an association between increased autoantibody production on-treatment with ICI and development of toxicity (Immune-related Adverse Events, irAEs). Conclusions We draw consensus for associations between class-switched B-cells and immune-active antibody isotypes that indicate heightened classical immunity, with improved immunotherapy response. While alternatively-activated, regulatory B-cells and immune-inert antibody isotypes associate with immunosuppression and less-favourable clinical outcomes. We reveal aspects of humoral immunity that offer opportunities to identify predictive biomarkers of immunotherapy response and irAEs.
Booth et al. (Wed,) studied this question.