B cell profiles, antibody repertoire and reactivity reveal dysregulated responses with autoimmune features in melanoma

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

Cited by 4 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3