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dc.contributor.authorHarris, RJ
dc.contributor.authorCheung, A
dc.contributor.authorNg, JCF
dc.contributor.authorLaddach, R
dc.contributor.authorChenoweth, AM
dc.contributor.authorCrescioli, S
dc.contributor.authorFittall, M
dc.contributor.authorDominguez Rodriguez, D
dc.contributor.authorRoberts, J
dc.contributor.authorLevi, D
dc.contributor.authorLiu, F
dc.contributor.authorAlberts, E
dc.contributor.authorQuist, J
dc.contributor.authorSantaolalla, A
dc.contributor.authorPinder, SE
dc.contributor.authorGillett, C
dc.contributor.authorHammar, N
dc.contributor.authorIrshad, S
dc.contributor.authorVan Hemelrijck, M
dc.contributor.authorDunn-Walters, DK
dc.contributor.authorFraternali, F
dc.contributor.authorSpicer, JF
dc.contributor.authorLacy, KE
dc.contributor.authorTsoka, S
dc.contributor.authorGrigoriadis, A
dc.contributor.authorTutt, ANJ
dc.contributor.authorKaragiannis, SN
dc.date.accessioned2021-08-19T14:14:08Z
dc.date.available2022-06-15T00:00:00Z
dc.date.issued2021-06-15
dc.identifier.citationCancer research, 2021
dc.identifier.issn0008-5472
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/4767
dc.identifier.eissn1538-7445
dc.identifier.eissn1538-7445en_US
dc.identifier.doi10.1158/0008-5472.can-20-3773
dc.identifier.doi10.1158/0008-5472.can-20-3773en_US
dc.description.abstractIn breast cancer, humoral immune responses may contribute to clinical outcomes, especially in more immunogenic subtypes. Here we investigated B lymphocyte subsets, immunoglobulin expression, and clonal features in breast tumors, focusing on aggressive triple-negative breast cancers (TNBC). In samples from TNBC patients and healthy volunteers, circulating and tumor-infiltrating B lymphocyte (TIL-B) were evaluated. CD20+CD27+IgD- isotype-switched B lymphocytes were increased in tumors, compared with matched blood. TIL-B frequently formed stromal clusters with T lymphocytes and engaged in bidirectional functional crosstalk, consistent with gene signatures associated with lymphoid assembly, co-stimulation, cytokine-cytokine receptor interactions, cytotoxic T cell activation, and T cell-dependent B cell activation. TIL-B upregulated B cell receptor (BCR) pathway molecules FOS and JUN, germinal center chemokine regulator RGS1, activation marker CD69, and TNFα signal transduction via NFκB, suggesting BCR-immune complex formation. Expression of genes associated with B lymphocyte recruitment and lymphoid assembly, including CXCL13, CXCR4, DC-LAMP, was elevated in TNBC compared with other subtypes and normal breast. TIL-B-rich tumors showed expansion of IgG but not IgA isotypes, and IgG isotype-switching positively associated with survival outcomes in TNBC. Clonal expansion was biased towards IgG, showing expansive clonal families with specific variable region gene combinations and narrow repertoires. Stronger positive selection pressure was present in the complementary determining regions (CDRs) of IgG compared to their clonally related IgA in tumor samples. Overall, class-switched B lymphocyte lineage traits were conspicuous in TNBC, associated with improved clinical outcomes, and conferred IgG-biased, clonally expanded, and likely antigen-driven humoral responses.
dc.formatPrint-Electronic
dc.languageeng
dc.language.isoeng
dc.rights.urihttp://www.rioxx.net/licenses/under-embargo-all-rights-reserved
dc.titleTumor-Infiltrating B Lymphocyte Profiling Identifies IgG-Biased, Clonally Expanded Prognostic Phenotypes In Triple-Negative Breast Cancer.
dc.typeJournal Article
dcterms.dateAccepted2021-06-14
rioxxterms.versionAM
rioxxterms.versionofrecord10.1158/0008-5472.can-20-3773
rioxxterms.licenseref.startdate2021-06-15
rioxxterms.licenseref.startdate2021-06-15en_US
dc.relation.isPartOfCancer research
pubs.notes12 months
pubs.organisational-group/ICR
pubs.organisational-group/ICR
pubs.publication-statusPublished
pubs.embargo.terms12 months
pubs.embargo.date2022-06-15T00:00:00Z
pubs.embargo.date2022-06-15T00:00:00Z
dc.contributor.icrauthorTutt, Andrewen


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