Circulating B cell and T cell activation states predict clinical outcomes in melanoma and reveal dynamic immune reinvigoration with checkpoint inhibitor immunotherapy
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Le résumé fourni par la source
BACKGROUND: Nearly half of patients with melanoma do not respond to immune checkpoint inhibitors (CPIs) and many develop immune-related adverse events (irAEs), often forcing treatment discontinuation, and underscoring the need to predict and monitor outcomes. Responses may depend on both B cell and T cell activity. METHODS: We performed high-dimensional mass cytometry profiling of coexisting peripheral B cell and key T cell states in treatment-naïve patients and healthy individuals, and paired longitudinal samples from CPI-treated patients, with clinical annotations to define immune correlates of outcomes. RESULTS: CPI-naive patients exhibited reduced CD19+ B cells, reduced B cell (CD21, IL-2, CXCR5) and T cell (CD38, CD27) activation markers, alongside enriched naïve (CD21lo) and double-negative (DN2)-like B cells, CD95+IL-10+plasmablasts, consistent with extrafollicular responses. Concurrently, programmed cell death protein 1 (PD-1)+ and proliferation marker protein-67 (Ki67)+ T cell expansion indicates ongoing activation with features of proliferative exhaustion. Active disease featured increased regulatory CD95 expression on B cells and expanded T follicular helper-like and activated DN (CD4-CD8-) T cells, indicating sustained antigen stimulation. Pretreatment, elevated PD-1+ T cells predicted irAEs, whereas VEGF (vascular endothelial growth factor)+TGF-β (transforming growth factor-β)+ DN T cells were enriched in patients without subsequent toxicity. Pretreatment, plasmablasts, transitional B cells, Forkhead box protein P3 (FoxP3)+ and central memory-like CD8+ T cells correlated with worse overall survival; naïve CD21lo B cells, PD-1+CD8+ T cells and CD4+follicular helper-like T cells predicted shorter event-free survival; CD4+ memory T cells predicted better prognosis, implicating dysregulated differentiation and sustained activation in adverse outcomes. On-treatment, naïve CD21hi B cells, plasmablasts, activated CD8+ and central memory-like CD4+ T cells expanded, indicating de novo humoral responses and cytotoxic T cell invigoration. On-treatment, increased class-switched memory (IgG2+) B and activated T cells predicted improved survival, while persistent naïve and DN B cells were associated with poorer outcomes. Anti-PD-1 monotherapy expanded naïve (CD21hi) B cells and global T cells. Anti-PD-1/anti-LAG-3 (lymphocyte-activation gene 3) combination contracted memory B cells. CONCLUSIONS: Melanoma displays aberrant peripheral B and T cell activation, maturation and exhaustion, prominent in active disease. Treatment-induced class-switched B cells and T cell invigoration predict clinical benefit and naïve/DN B cells signify resistance. Coordinated B and T cell responses, especially recurrent extrafollicular B cell and exhausted/regulatory T cell states emerge as candidate indicators of outcome.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Circulating B cell and T cell activation states predict clinical outcomes in melanoma and reveal dynamic immune reinvigoration with checkpoint inhibitor immunotherapy
- Date Crossref
- 01/08/2026
- Éditeur
- BMJ
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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King's College London Centre for Gene Therapy and Regenerative Medicine pays non établi dans la noticeUniversité ou école supérieure
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Cell and Gene Therapy Catapult pays non établi dans la noticeStructure de recherche
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Guy's and St Thomas' NHS Foundation Trust R&D Department pays non établi dans la noticeÉtablissement de santé
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Breast Cancer Now pays non établi dans la noticeOrganisation à but non lucratif
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Moorfields Eye Hospital NHS Foundation Trust Adnexal Department pays non établi dans la noticeÉtablissement de santé
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Moorfields Eye Hospital pays non établi dans la noticeÉtablissement de santé
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University College London pays non établi dans la noticeUniversité ou école supérieure
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Queen Mary University of London Barts Cancer Institute pays non établi dans la noticeUniversité ou école supérieure
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Barts Cancer Institute pays non établi dans la noticeUniversité ou école supérieure
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Faculty of Natural Department of Informatics pays non établi dans la noticeUniversité ou école supérieure
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School of Basic and Medical Biosciences and KHP Centre for Translational Medicine St. John’s Institute of Dermatology pays non établi dans la noticeUniversité ou école supérieure
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Centre for Gene Therapy and Regenerative Medicine — King's College London, Cell and Gene Therapy Catapult et R&D Department — Guy's and St Thomas' NHS Foundation Trust, avec 9 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.