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

Silvia Crescioli, Isabel Correa, Joseph Ng, Zena N. Willsmore, Roman Laddach, Alicia Chenoweth, Jitesh Chauhan, Ashley Meo, Alexander Stewart, Eleni Kalliolia, Elena Alberts, Rebecca Adams, Robert J. Harris, Silvia Mele, Giulia Pellizzari, Anna B. M. Black, Heather J. Bax, Anthony Cheung, Mano Nakamura, Ricarda M. Hoffmann, Manuela Terranova-Barberio, Niwa Ali, Ihor Batruch, Antoninus Soosaipillai, Ioannis Prassas, Antigona Ulndreaj, Miyo K. Chatanaka, Rosamund Nuamah, Shichina Kannambath, Pawan Dhami, Jenny L. C. Geh, Alastair D. MacKenzie Ross, Ciaran Healy, Anita Grigoriadis, David Kipling, Panagiotis Karagiannis, Deborah K. Dunn-Walters, Eleftherios P. Diamandis, Sophia Tsoka, James Spicer, Katie E. Lacy, Franca Fraternali and Sophia N. Karagiannis ()
Additional contact information
Silvia Crescioli: King’s College London, Guy’s Hospital
Isabel Correa: King’s College London, Guy’s Hospital
Joseph Ng: King’s College London
Zena N. Willsmore: King’s College London, Guy’s Hospital
Roman Laddach: King’s College London, Guy’s Hospital
Alicia Chenoweth: King’s College London, Guy’s Hospital
Jitesh Chauhan: King’s College London, Guy’s Hospital
Ashley Meo: Mount Sinai Hospital
Alexander Stewart: University of Surrey
Eleni Kalliolia: King’s College London, Guy’s Hospital
Elena Alberts: King’s College London, Guy’s Hospital
Rebecca Adams: King’s College London, Guy’s Hospital
Robert J. Harris: King’s College London, Guy’s Hospital
Silvia Mele: King’s College London, Guy’s Hospital
Giulia Pellizzari: King’s College London, Guy’s Hospital
Anna B. M. Black: King’s College London, Guy’s Hospital
Heather J. Bax: King’s College London, Guy’s Hospital
Anthony Cheung: King’s College London, Guy’s Hospital
Mano Nakamura: King’s College London, Guy’s Hospital
Ricarda M. Hoffmann: King’s College London, Guy’s Hospital
Manuela Terranova-Barberio: King’s College London, Guy’s Hospital
Niwa Ali: King’s College London
Ihor Batruch: Mount Sinai Hospital
Antoninus Soosaipillai: Mount Sinai Hospital
Ioannis Prassas: Mount Sinai Hospital
Antigona Ulndreaj: Mount Sinai Hospital
Miyo K. Chatanaka: Mount Sinai Hospital
Rosamund Nuamah: Guy’s and St. Thomas’ NHS Foundation Trust
Shichina Kannambath: Guy’s and St. Thomas’ NHS Foundation Trust
Pawan Dhami: Guy’s and St. Thomas’ NHS Foundation Trust
Jenny L. C. Geh: St John’s Institute of Dermatology, Guy’s, King’s, and St. Thomas’ Hospitals NHS Foundation Trust
Alastair D. MacKenzie Ross: Department of Plastic Surgery at Guy’s and St. Thomas’ NHS Foundation Trust
Ciaran Healy: Department of Plastic Surgery at Guy’s and St. Thomas’ NHS Foundation Trust
Anita Grigoriadis: King’s College London, Guy’s Hospital
David Kipling: University of Surrey
Panagiotis Karagiannis: King’s College London, Guy’s Hospital
Deborah K. Dunn-Walters: University of Surrey
Eleftherios P. Diamandis: Mount Sinai Hospital
Sophia Tsoka: King’s College London
James Spicer: King’s College London, Guy’s Hospital
Katie E. Lacy: King’s College London, Guy’s Hospital
Franca Fraternali: King’s College London
Sophia N. Karagiannis: King’s College London, Guy’s Hospital

Nature Communications, 2023, vol. 14, issue 1, 1-21

Abstract: Abstract B 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.

Date: 2023
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DOI: 10.1038/s41467-023-39042-y

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