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Record W4379878284 · doi:10.1038/s41467-023-39042-y

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

2023· article· en· W4379878284 on OpenAlexaff
Silvia Crescioli, Isabel Corrêa, Joseph Ng, Zena Willsmore, Roman Laddach, Alicia M. Chenoweth, Jitesh Chauhan, Ashley Di Meo, Alexander Stewart, Eleni Kalliolia, Rebecca Adams, R. J. C. Harris, Silvia Mele, Giulia Pellizzari, Anna 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, Sophia N. Karagiannis

Bibliographic record

VenueNature Communications · 2023
Typearticle
Languageen
FieldImmunology and Microbiology
TopicImmunotherapy and Immune Responses
Canadian institutionsUniversity Health NetworkUniversity of TorontoLunenfeld-Tanenbaum Research InstituteMount Sinai Hospital
FundersGuy's and St Thomas' NHS Foundation TrustMenzies Centre for Australian Studies, King's College London, University of LondonBiotechnology and Biological Sciences Research CouncilMedical Research CouncilKing's Health PartnersKing's College LondonGuy's and St Thomas' CharityRotary FoundationCancer Research UKNational Institute for Health and Care ResearchBreast Cancer Now
KeywordsAntibodyRepertoireMelanomaImmunologyComputational biologyCellBiologyMedicineCancer researchGenetics

Abstract

fetched live from OpenAlex

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.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.901
Threshold uncertainty score0.894

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.001
Science and technology studies0.0010.001
Scholarly communication0.0000.000
Open science0.0010.000
Research integrity0.0010.002
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.011
GPT teacher head0.281
Teacher spread0.270 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations41
Published2023
Admission routes1
Has abstractyes

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