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Record W3197804636 · doi:10.1084/jem.20200853

Autoimmunity affecting the biliary tract fuels the immunosurveillance of cholangiocarcinoma

2021· article· en· W3197804636 on OpenAlexafffund
Juliette Paillet, Céleste Plantureux, Sarah Lévesque, Julie Le Naour, Gautier Stoll, Allan Sauvat, Pamela Caudana, Jimena Tosello, Norma Bloy, Sylvie Lachkar, Isabelle Martins, Paule Opolon, Andrea Checcoli, Agathe Delaune, Noémie Robil, Pierre de la Grange, Juliette Hamroune, Franck Letourneur, Gwennhaël Autret, Patrick S.C. Leung, M. Eric Gershwin, Jie Zhu, Mark J. Kurth, Bouchra Lekbaby, Jérémy Augustin, Youra Kim, Shashi Gujar, Cédric Coulouarn, Laura Fouassier, Laurence Zitvogel, Eliane Piaggio, Chantal Housset, Patrick Soussan, Maria Chiara Maiuri, Guido Kroemer, Jonathan Pol

Bibliographic record

VenueThe Journal of Experimental Medicine · 2021
Typearticle
Languageen
FieldMedicine
TopicLiver Diseases and Immunity
Canadian institutionsBeatrice Hunter Cancer Research InstituteDalhousie University
FundersHigh-end Foreign Experts Recruitment Plan of ChinaLabex Immuno-OncologyEuropean Research Area Network on Cardiovascular DiseasesDalhousie Medical Research FoundationChancellerie des Universités de ParisInstitut Universitaire de FranceLabexLigue Contre le CancerFondation pour la Recherche MédicaleHorizon 2020 Framework ProgrammeFondation de l'Avenir pour la Recherche Médicale AppliquéeCancéropôle Ile de FranceDalhousie UniversityInstitut National Du CancerInstitut National de la Santé et de la Recherche MédicaleInstitut Gustave-RoussyAgence Nationale de la RechercheFondation LeducqCanadian HIV Trials Network, Canadian Institutes of Health ResearchCanadian Cancer SocietyCanadian Institutes of Health ResearchAssociation pour la Recherche sur le CancerSeerave FoundationEuropean CommissionE-Rare
KeywordsImmunosurveillanceAutoimmunityContext (archaeology)Biliary tractImmunologyPrimary sclerosing cholangitisCancer researchBiologyMedicineImmune systemPathologyInternal medicine

Abstract

fetched live from OpenAlex

Cholangiocarcinoma (CCA) results from the malignant transformation of cholangiocytes. Primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC) are chronic diseases in which cholangiocytes are primarily damaged. Although PSC is an inflammatory condition predisposing to CCA, CCA is almost never found in the autoimmune context of PBC. Here, we hypothesized that PBC might favor CCA immunosurveillance. In preclinical murine models of cholangitis challenged with syngeneic CCA, PBC (but not PSC) reduced the frequency of CCA development and delayed tumor growth kinetics. This PBC-related effect appeared specific to CCA as it was not observed against other cancers, including hepatocellular carcinoma. The protective effect of PBC was relying on type 1 and type 2 T cell responses and, to a lesser extent, on B cells. Single-cell TCR/RNA sequencing revealed the existence of TCR clonotypes shared between the liver and CCA tumor of a PBC host. Altogether, these results evidence a mechanistic overlapping between autoimmunity and cancer immunosurveillance in the biliary tract.

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)0.002
metaresearch head score (Gemma)0.001
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 score0.751
Threshold uncertainty score0.480

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0020.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.001
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
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 head0.029
GPT teacher head0.309
Teacher spread0.280 · 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

Citations42
Published2021
Admission routes2
Has abstractyes

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