ArticleJournal for immunotherapy of cancer2025
Circulating immunoregulatory B cell and autoreactive antibody profiles predict lack of toxicity to anti-PD-1 checkpoint inhibitor treatment in advanced melanoma.
Article in Journal for immunotherapy of cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.
What it found
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
11 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Pooled it
- B cells and humoral immunity in melanoma: regulatory and autoimmune-like features and implications for immunotherapy.Oncoimmunology · 2026Review
- Tumor-infiltrating B cells evolve towards interferon-rich trajectories aligned with immunotherapy in melanoma.Journal of experimental & clinical cancer research : CR · 2026Article
- Circulating B cell and T cell activation states predict clinical outcomes in melanoma and reveal dynamic immune reinvigoration with checkpoint inhibitor immunotherapy.Journal for immunotherapy of cancer · 2026Article
- Interferon-Mediated Regulation of Memory B Cell Identity and Function.Immunological reviews · 2026Review
- Phenotypic, functional, prognostic and predictive significance of B-cell and antibody responses in human melanoma: a scoping review.The British journal of dermatology · 2026Article
- From inflammatory initiation to fibrotic remodeling: mechanisms and precision therapeutic strategies in otorhinolaryngologic involvement of IgG4-related disease.Frontiers in medicine · 2026Review
- Integrated cellular, proteomic and metabolomic profiling of immune-related adverse events in non-small cell lung cancer.Frontiers in immunology · 2026Article
- The Search for Predictive Biomarkers in Response to Immune Checkpoint Inhibitors and Associated Adverse Events.Journal of personalized medicine · 2025Review
- Review
- Hematologic immune-related adverse events in skin cancer patients treated with immune checkpoint inhibitors: a case series.Frontiers in pharmacology · 2025Article
Corrections and comments
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Authors and funding
20 authors.
Funding
Abstract
backgroundThe majority of patients with melanoma develop immune-related adverse events (irAEs), and over half do not respond to anti-PD-1 (Programmed cell death protein 1) checkpoint inhibitor (CPI) immunotherapy. Accurate predictive biomarkers for both response to therapy and development of irAEs are currently lacking in clinical practice. Here, we conduct deep immunophenotyping of circulating regulatory and class-switched B cell and antibody immune states in patients with advanced stage III/IV melanoma prior to and longitudinally during CPI.
methodsMass cytometry, serum antibody isotyping and immuno-mass spectrometry proteome-wide screening evaluations to identify autoreactive antibodies were undertaken to profile circulating humoral immunity features in patients and healthy subjects and interrogate pretreatment B cell and antibody signatures that predict toxicity and response to anti-PD-1 therapy. In paired blood samples pretreatment and post-treatment, these humoral immune response profiles were monitored and correlated with the onset of toxicity.
resultsWe found increased circulating IL-10+ (Interleukin-10+) plasmablasts and double-negative (DN) B cell frequencies, higher PD-L1 (programmed death ligand 1), TGFβ (Transforming Growth Factorβ) and CD95 expression by B cells, alongside higher IgG4 and IgE serum levels in patients with stage III/IV melanoma. This suggests enhanced B regulatory and Th2 (Thelper2)-driven responses in advanced disease. Increased baseline frequency of DN2 B cells, plasmablasts, and serum IgE, IgA and antibody autoreactivity were observed in patients who did not develop irAE. During treatment, higher IL-10+class-switched memory B cell, plasmablast and IgG1, IgG3 and IgE, alongside reduced IgG2, IgG4, IgA and IgM levels, were observed. A reduction in autoantibodies targeting tubulins was observed during treatment. Increased frequency of class-switched memory B cells predicted improved survival, while reduced transitional and PD-L1+TGFβ+ naive B cell frequencies and higher IgG4 and IgE levels predicted lower survival, on anti-PD-1 therapy.
conclusionsDistinct B cell and antibody reactivities in patients with advanced melanoma share features with extrafollicular B cell responses in autoimmune diseases, may be protective from irAE and help predict outcomes to anti-PD-1.
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