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Record W2921210767 · doi:10.1158/2326-6066.cir-18-0517

A Transcriptionally Distinct CXCL13+CD103+CD8+ T-cell Population Is Associated with B-cell Recruitment and Neoantigen Load in Human Cancer

2019· article· en· W2921210767 on OpenAlexaff
Hagma H. Workel, Joyce M. Lubbers, Roland Arnold, Thalina M. Prins, Pieter van der Vlies, Kim de Lange, Tjalling Bosse, Inge C. van Gool, Florine A. Eggink, Maartje C.A. Wouters, Fenne L. Komdeur, Elisabeth C. van der Slikke, Carien L. Creutzberg, Arjan Kol, Annechien Plat, Mark A. Glaire, David N. Church, Hans W. Nijman, Marco de Bruyn

Bibliographic record

VenueCancer Immunology Research · 2019
Typearticle
Languageen
FieldMedicine
TopicCancer Immunotherapy and Biomarkers
Canadian institutionsUniversity of Victoria
FundersUniversitair Medisch Centrum GroningenWellcome TrustMinistry of Earth SciencesAcademy of Medical SciencesKWF KankerbestrijdingNational Institute for Health and Care ResearchJan Kornelis de Cock Stichting
KeywordsCXCL13CD8BiologyB cellImmunologyT cellTumor microenvironmentCancer researchAcquired immune systemChemokineCXCR5Immune systemPopulationAntibodyChemokine receptorMedicine

Abstract

fetched live from OpenAlex

Abstract The chemokine CXCL13 mediates recruitment of B cells to tumors and is essential for the formation of tertiary lymphoid structures (TLSs). TLSs are thought to support antitumor immunity and are associated with improved prognosis. However, it remains unknown whether TLSs are formed in response to the general inflammatory character of the tumor microenvironment, or rather, are induced by (neo)antigen-specific adaptive immunity. We here report on the finding that the TGFβ-dependent CD103+CD8+ tumor-infiltrating T-cell (TIL) subpopulation expressed and produced CXCL13. Accordingly, CD8+ T cells from peripheral blood activated in the presence of TGFβ upregulated CD103 and secreted CXCL13. Conversely, inhibition of TGFβ receptor signaling abrogated CXCL13 production. CXCL13+CD103+CD8+ TILs correlated with B-cell recruitment, TLSs, and neoantigen burden in six cohorts of human tumors. Altogether, our findings indicated that TGFβ plays a noncanonical role in coordinating immune responses against human tumors and suggest a potential role for CXCL13+CD103+CD8+ TILs in mediating B-cell recruitment and TLS formation in human tumors.

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 machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.003
Threshold uncertainty score0.009

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0030.000

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 head0.092
GPT teacher head0.387
Teacher spread0.294 · 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 source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
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

Citations262
Published2019
Admission routes1
Has abstractyes

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