MétaCan
Menu
← Back to cohort
Record W4400931289 · doi:10.1101/2024.07.22.24310819

Spatially-resolved tumour infiltrating immune cells and prognosis in breast cancer

2024· preprint· en· W4400931289 on OpenAlexaff
Aaron J. Bernstein, Renske Keeman, Amber N. Hurson, Fiona M. Blows, Manjeet K. Bolla, Jodi L. Miller, Roger L. Milne, Hugo M. Horlings, Alexandra J. van den Broek, Clara Bodelón, James M. Hodge, Alpa V Patel, Lauren R. Teras, Federico Canzian, Rudolf Kaaks, Hermann Brenner, Ben Schoettker, Sabine Behrens, Jenny Chang‐Claude, Tabea Maurer, Nadia Obi, Fergus J. Couch, Hasan Ali, Carlos Caldas, Irene L. Andrulis, Gord Glendon, Anna Marie Mulligan, Wilma E. Mesker, Agnes Jager, Annette Heemskerk-Gerritsen, Peter Devilee, Scott M. Lawrence, Jolanta Lissowska, Karun Mutreja, Thomas Ahearn, Stephen Chanock, Máire A. Duggan, Diana Eccles, J. Louise Jones, William Tapper, Antoinette Hollestelle, Maartje J. Hooning, John W.M. Martens, Carolien H. M. van Deurzen, Angela Cox, Simon S. Cross, Mikael Hartman, Jingmei Li, Thomas Choudary Putti, Ute Hamann, Anna Jakubowska, Nicki J Camp, Melissa H. Cessna, Amy Berrington de González, Katarzyna Białkowska, Jacek Gronwald, Jan Lubi ski, Siddhartha Yadav, Píetro Lió, Doug F. Easton, Mustapha Abubakar, Montserrat García‐Closas, Paul D.P. Pharoah, Marjanka K. Schmidt

Bibliographic record

VenuemedRxiv · 2024
Typepreprint
Languageen
FieldMedicine
TopicCancer Immunotherapy and Biomarkers
Canadian institutionsUniversity of TorontoUniversity Health NetworkSinai Health SystemUniversity of CalgaryLunenfeld-Tanenbaum Research Institute
FundersNational Institute for Health and Care Research
KeywordsCD20Immune systemBreast cancerMedicineStromal cellCD163FOXP3Internal medicineTissue microarrayCD8OncologyCD68CancerPathologyImmunohistochemistryImmunologyBiologyGene

Abstract

fetched live from OpenAlex

Background The immune response in breast tumors has an important role in prognosis, but the role of spatial localization of immune cells and of interaction between subtypes is not well characterized. We evaluated the association between spatially resolved tissue infiltrating immune cells (TIICs) and breast cancer specific survival (BCSS) in a large multicenter study. Patients and methods Tissue microarrays with tumor cores from 17,265 breast cancer patients of European descent were stained for CD8, FOXP3, CD20, and CD163. We developed a machine learning based tissue segmentation and immune cell detection algorithm using Halo to score each image for the percentage of marker positive cells by compartment (overall, stroma, or tumor). We assessed the association between log transformed TIIC scores and BCSS using Cox regression. Results Total CD8+ and CD20+ TIICs (stromal and intra-tumoral) were associated with better BCSS in women with ER-negative (HR per standard deviation = 0.91 [95% CI 0.85 - 0.98] and 0.89 [0.84 - 0.94] respectively) and ER-positive disease (HR = 0.92 [95% CI 0.87 - 0.98] and 0.93 [0.86 - 0.99] respectively) in multi-marker models. In contrast, CD163+ macrophages were associated with better BCSS in ER-negative disease (0.94 [0.87 - 1.00]) and a poorer BCSS in ER-positive disease 1.04 [0.99 - 1.10]. There was no association between FOXP3 and BCSS. The observed associations tended to be stronger for intra-tumoral than stromal compartments for all markers. However, the TIIC markers account for only 7.6 percent of the variation in BCSS explained by the multi-marker fully-adjusted model for ER-negative cases and 3.0 percent for ER-positive cases. Conclusions The presence of intra-tumoral and stromal TIICs is associated with better BCSS in both ER-negative and ER-positive breast cancer. This may have implications for the use of immunotherapy. However, the addition of TIICs to existing prognostic models would only result in a small improvement in model performance.

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)0.001
metaresearch head score (Gemma)0.002
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: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.001
Threshold uncertainty score0.005

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.002
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.001
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 head0.017
GPT teacher head0.277
Teacher spread0.260 · 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

Citations0
Published2024
Admission routes1
Has abstractyes

Explore more

Same venuemedRxiv→Same topicCancer Immunotherapy and Biomarkers→French-language works237,207→