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B cells and humoral immunity in melanoma: regulatory and autoimmune-like features and implications for immunotherapy - PubMed

5 days ago
  • #immunotherapy
  • #melanoma
  • #B cells
  • B cells and humoral immunity play a critical role in melanoma progression and immunotherapy outcomes.
  • Checkpoint inhibitor (CPI) therapy primarily targets T cells, but B cell biology is also clinically relevant in melanoma.
  • Dysregulated B cell subsets, including naïve and immunosuppressive populations, correlate with poor survival.
  • Regulatory B cells (Bregs) contribute to immune tolerance by inducing regulatory T cells (Tregs) and secreting immunosuppressive cytokines (TGFβ and IL-10).
  • Intratumoral B cells show clonal expansion, somatic hypermutation, and polyreactivity, but may also exhibit unproductive sequences.
  • Mature class-switched memory B cells and tumor-resident B cells in tertiary lymphoid structures (TLSs) are linked to improved CPI responses.
  • Dynamic changes in circulating B cell phenotypes and autoantibody profiles during CPI treatment relate to therapeutic efficacy and immune-related adverse events (irAEs).
  • B cells have a dual role in melanoma, supporting antitumor immunity or promoting immune escape.
  • Potential strategies include targeting Bregs, correcting isotype imbalance, and using B cell signatures as biomarkers.
  • Monitoring humoral responses before and during CPI therapy may improve patient stratification and predict toxicity.