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.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: