MétaCan
Menu
Back to cohort
Record W4383815012 · doi:10.1016/j.ccell.2023.06.006

Tumor monocyte content predicts immunochemotherapy outcomes in esophageal adenocarcinoma

2023· article· en· W4383815012 on OpenAlexaff
Joseph A. Chadwick, Richard Owen, Michael J. White, Joseph Kaplinsky, Iliana Peneva, Anna Frangou, Phil F. Xie, Jaeho Chang, Andrew Roth, Bob Amess, Sabrina A. James, Margarida Rei, Hannah S. Fuchs, Katy J. McCann, Ayo O. Omiyale, Brittany‐Amber Jacobs, Simon Lord, Stewart Norris-Bulpitt, Sam T. Dobbie, Lucinda Griffiths, Kristen Aufiero Ramirez, Toni Ricciardi, Mary Macri, Aileen Ryan, Ralph Venhaus, Benoı̂t J. Van den Eynde, Ioannis Karydis, Benjamin Schuster‐Böckler, Mark R. Middleton, Xin Lü, David Ahern, G. Berridge, Jingfei Cheng, Magdalena Dróżdż, Román Fischer, Masato Inoue, Benedikt M. Kessler, Hantao Lou, Naomi McGregor, Chansavath Phetsouphanh, Carlos Ruiz de Alegría Puig, Paulina Siejka-Zielińska, Chunxiao Song, Markéta Tomková, Gergana Velikova

Bibliographic record

VenueCancer Cell · 2023
Typearticle
Languageen
FieldMedicine
TopicEsophageal Cancer Research and Treatment
Canadian institutionsUniversity of British Columbia
FundersCancer Research UKNational Institute for Health and Care ResearchLudwig Institute for Cancer ResearchAstraZeneca
KeywordsMedicineEsophageal cancerOncologyInternal medicineTranscriptomeAdenocarcinomaCancer researchCancerBiologyGeneGene expression

Abstract

fetched live from OpenAlex

For inoperable esophageal adenocarcinoma (EAC), identifying patients likely to benefit from recently approved immunochemotherapy (ICI+CTX) treatments remains a key challenge. We address this using a uniquely designed window-of-opportunity trial (LUD2015-005), in which 35 inoperable EAC patients received first-line immune checkpoint inhibitors for four weeks (ICI-4W), followed by ICI+CTX. Comprehensive biomarker profiling, including generation of a 65,000-cell single-cell RNA-sequencing atlas of esophageal cancer, as well as multi-timepoint transcriptomic profiling of EAC during ICI-4W, reveals a novel T cell inflammation signature (INCITE) whose upregulation correlates with ICI-induced tumor shrinkage. Deconvolution of pre-treatment gastro-esophageal cancer transcriptomes using our single-cell atlas identifies high tumor monocyte content (TMC) as an unexpected ICI+CTX-specific predictor of greater overall survival (OS) in LUD2015-005 patients and of ICI response in prevalent gastric cancer subtypes from independent cohorts. Tumor mutational burden is an additional independent and additive predictor of LUD2015-005 OS. TMC can improve patient selection for emerging ICI+CTX therapies in gastro-esophageal cancer.

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)0.000
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: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.044
Threshold uncertainty score0.715

Codex and Gemma teacher scores by category

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)0.0010.000

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 head0.057
GPT teacher head0.331
Teacher spread0.274 · 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 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

Citations51
Published2023
Admission routes1
Has abstractyes

Explore more

Same venueCancer CellSame topicEsophageal Cancer Research and TreatmentFrench-language works237,207