B cell profiles, antibody repertoire and reactivity reveal dysregulated responses with autoimmune features in melanoma
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Published:2023-06-08
Issue:1
Volume:14
Page:
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ISSN:2041-1723
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Container-title:Nature Communications
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language:en
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Short-container-title:Nat Commun
Author:
Crescioli Silvia, Correa Isabel, Ng JosephORCID, Willsmore Zena N., Laddach Roman, Chenoweth Alicia, Chauhan Jitesh, Di Meo Ashley, Stewart Alexander, Kalliolia Eleni, Alberts Elena, Adams Rebecca, Harris Robert J., Mele Silvia, Pellizzari GiuliaORCID, Black Anna B. M., Bax Heather J.ORCID, Cheung AnthonyORCID, Nakamura ManoORCID, Hoffmann Ricarda M., Terranova-Barberio Manuela, Ali Niwa, Batruch Ihor, Soosaipillai Antoninus, Prassas Ioannis, Ulndreaj Antigona, Chatanaka Miyo K., Nuamah Rosamund, Kannambath Shichina, Dhami PawanORCID, Geh Jenny L. C.ORCID, MacKenzie Ross Alastair D.ORCID, Healy Ciaran, Grigoriadis AnitaORCID, Kipling David, Karagiannis Panagiotis, Dunn-Walters Deborah K., Diamandis Eleftherios P.ORCID, Tsoka Sophia, Spicer JamesORCID, Lacy Katie E., Fraternali FrancaORCID, Karagiannis Sophia N.ORCID
Abstract
AbstractB cells are known to contribute to the anti-tumor immune response, especially in immunogenic tumors such as melanoma, yet humoral immunity has not been characterized in these cancers to detail. Here we show comprehensive phenotyping in samples of circulating and tumor-resident B cells as well as serum antibodies in melanoma patients. Memory B cells are enriched in tumors compared to blood in paired samples and feature distinct antibody repertoires, linked to specific isotypes. Tumor-associated B cells undergo clonal expansion, class switch recombination, somatic hypermutation and receptor revision. Compared with blood, tumor-associated B cells produce antibodies with proportionally higher levels of unproductive sequences and distinct complementarity determining region 3 properties. The observed features are signs of affinity maturation and polyreactivity and suggest an active and aberrant autoimmune-like reaction in the tumor microenvironment. Consistent with this, tumor-derived antibodies are polyreactive and characterized by autoantigen recognition. Serum antibodies show reactivity to antigens attributed to autoimmune diseases and cancer, and their levels are higher in patients with active disease compared to post-resection state. Our findings thus reveal B cell lineage dysregulation with distinct antibody repertoire and specificity, alongside clonally-expanded tumor-infiltrating B cells with autoimmune-like features, shaping the humoral immune response in melanoma.
Funder
Cancer Research UK Breast Cancer Now Guy’s and St Thomas’ Charity King’s Health Partners | Guy’s and St Thomas’ NHS Foundation Trust
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry,Multidisciplinary
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