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    Tumour infiltrating B cells discriminate checkpoint blockade-induced responses

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    Authors
    Valpione, Sara
    Campana, L. G.
    Weightman, John
    Salih, Zena
    Galvani, Elena
    Mundra, Piyushkumar A
    De Rosa, F.
    Gupta, Avinash
    Serra-Bellver, Patricio
    Lorigan, Paul C
    Germetaki, Theodora
    Dynowski, Marek
    Kitcatt, Stephen
    Sahoo, Sudhakar
    Lee, Dave
    Dhomen, Nathalie
    Lord, G.
    Marais, Richard
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    Affiliation
    Molecular Oncology Group, Cancer Research UK Manchester Institute, The University of Manchester, Alderley Park SK10 4TG, United Kingdom; The Christie NHS Foundation Trust, 550 Wilmslow Road, Manchester M20 4BX, United Kingdom.
    Issue Date
    2022
    
    Metadata
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    Abstract
    Background: Immune cell-driven anti-cancer activity is paramount for effective responses to checkpoint inhibitors (ICB). However, the contribution of the different immune cell subsets in the circulation and within the tumour is poorly understood. Materials and methods: To elucidate the role of the different cell subsets in anti-tumour responses elicited by ICB, we performed single-cell analysis of the transcriptome and surface proteome of paired pre- and early on-treatment metastatic melanoma tumour biopsies and matched peripheral blood mononuclear cell samples. We next compared the survival of metastatic melanoma patients treated with ICB according to the abundance of pre-treatment tumour-infiltrating B cell clonotypes. Results: We identified cell clusters associated with disease control or progression, defined differential expression of biological pathways likely involved in the immune awakening against the tumour and examined how cell-cell communication patterns between the tumour cell subsets change during treatment. Furthermore, we discovered that B cells (immunoglobulin expression and abundance of B cell clonotypes) discriminate the clinical response after ICB and propose that B cells likely contribute to anti-tumour immunity by antigen presentation through major histocompatibility complex molecules. Finally, we demonstrated that the abundance of tumour-infiltrating B cell clonotypes at baseline identifies two distinct risk groups, a finding that we confirmed in an independent cohort. Conclusions: Our exploratory translational study provides new insights on the mechanistic role of B cells in anti-melanoma immunity during treatment with ICB. Additionally, we support pre-treatment B cell tumour infiltration as a promising prognostic biomarker to be further validated as a tool for clinical risk stratification.
    Citation
    Valpione S, Campana LG, Weightman J, Salih Z, Galvani E, Mundra PA, et al. Tumour infiltrating B cells discriminate checkpoint blockade-induced responses. European journal of cancer (Oxford, England : 1990). 2022 Oct 5;177:164-74. PubMed PMID: 36347135. Epub 2022/11/09. eng.
    Journal
    European Journal of Cancer
    URI
    http://hdl.handle.net/10541/625763
    DOI
    10.1016/j.ejca.2022.09.022
    PubMed ID
    36347135
    Additional Links
    https://dx.doi.org/10.1016/j.ejca.2022.09.022
    Type
    Article
    Language
    en
    ae974a485f413a2113503eed53cd6c53
    10.1016/j.ejca.2022.09.022
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