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Altering the dendritic cell signature in the lung: a new adjuvant to immune checkpoint inhibitor therapies?

2020· article· en· W4313373133 on OpenAlexaff
Julyanne Brassard, Émilie Bernatchez, Meredith Elizabeth Gill, Philippe Joubert, Marie‐Renée Blanchet

Bibliographic record

VenueThe Journal of Immunology · 2020
Typearticle
Languageen
FieldMedicine
TopicCancer Immunotherapy and Biomarkers
Canadian institutionsInstitut universitaire de cardiologie et de pneumologie de Québec
Fundersnot available
KeywordsImmune systemCancer researchImmunotherapyLung cancerDendritic cellImmune checkpointTumor microenvironmentPopulationImmunologyAntigenT cellAntigen presentationCD8FOXP3MedicineBiologyOncology

Abstract

fetched live from OpenAlex

Abstract Lung cancer is the leading cause of cancer-related death. While the recent introduction of immune checkpoint immunotherapies significantly improves patient outcome, many do not respond to this treatment. Dendritic cells (DCs) activate CD8+ T cells to promote the anticancer immune response. Also, in mice, pulmonary CD103+ DC1s specialize in tumour antigen presentation. However, cancer induces an immunosuppressive microenvironment that alters immune function to promote tumor development. Yet, the impact of lung tumor development on DCs remains misunderstood. To study the impact of lung tumour development on the lung dendritic cell signature, Lewis lung carcinoma (LLC) and B16F10 cells (melanoma lung metastasis) were injected intravenously, and lung DC populations analysed by flow cytometry. We observed that in cancer, the proportions of CD103+ DC1 are largely reduced, while an uncharacterized lung CD103+CD11b+ DC population is induced. The latest express surface markers and transcription factors associated with the DC2 population and high levels of PD-L1 and PD-L2 regulatory molecules. This is of crucial importance to immune checkpoint inhibitor therapies, as they rely on the efficient presentation of tumour antigen by DCs to induce T cell responses. In order to promote the anti-tumor capacity of the DC signature, CD103+ DC1s were injected in combination with an immune checkpoint inhibitor (anti-PD-1) in the B16F10 model of resistance to anti-PD1 therapy. The co-injection led to improved sensitivity to immunotherapy. Thus, promoting the replenishment of an anticancer DC environment could be an interesting therapeutic avenue to increase the efficiency of existing immune checkpoint inhibitor therapies.

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: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.001
Threshold uncertainty score0.004

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 integrity0.0000.001
Insufficient payload (model declined to judge)0.0010.000

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 head0.016
GPT teacher head0.259
Teacher spread0.243 · 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 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

Citations2
Published2020
Admission routes1
Has abstractyes

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