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Record W4308544300 · doi:10.1016/j.ygyno.2022.10.022

Profiling the immune landscape in mucinous ovarian carcinoma

2022· article· en· W4308544300 on OpenAlexafffund
Nicola S. Meagher, Phineas T. Hamilton, Katy Milne, Shelby Thornton, Bronwyn Harris, Ashley Weir, Jennifer Alsop, Christiani Bisinoto, James D. Brenton, Angela Brooks‐Wilson, Derek S. Chiu, Kara L. Cushing‐Haugen, Sián Fereday, Dale W. Garsed, Simon A. Gayther, Aleksandra Gentry‐Maharaj, C. Blake Gilks, Mercedes Jimenez‐Liñan, Catherine J. Kennedy, Nhu D. Le, Anna Piskorz, Marjorie J. Riggan, Mitul Shah, Naveena Singh, Aline Talhouk, Martin Widschwendter, David D.L. Bowtell, Francisco José Cândido dos Reis, Linda S. Cook, Renée T. Fortner, María J. García, Holly R. Harris, David G. Huntsman, Anthony N. Karnezis, Martin Köbel, Usha Menon, Paul D.P. Pharoah, Jennifer A. Doherty, Michael S. Anglesio, Malcolm C. Pike, Celeste Leigh Pearce, Michael Friedländer, Anna DeFazio, Brad H. Nelson, Susan J. Ramus

Bibliographic record

VenueGynecologic Oncology · 2022
Typearticle
Languageen
FieldMedicine
TopicCancer Immunotherapy and Biomarkers
Canadian institutionsUniversity of CalgaryUniversity of British ColumbiaVancouver General HospitalCanada's Michael Smith Genome Sciences CentreFoothills Medical CentreBC Cancer Agency
FundersNational Cancer InstituteCancer Council TasmaniaNational Health and Medical Research CouncilMedical Research CouncilHorizon 2020 Framework ProgrammeOak FoundationBC Cancer FoundationCanada Research ChairsCancer Research SocietyConselho Nacional de Desenvolvimento Científico e TecnológicoCancer Council VictoriaUniversity of New South WalesCanadian Institutes of Health ResearchCancer Institute NSWEuropean CommissionCalgary Laboratory ServicesUniversity of CambridgeUniversity College LondonCancer Research UKMichael Smith Health Research BCFaculty of Medicine and Health, University of SydneyTranslational Cancer Research NetworkEuropean Regional Development FundBundesministerium für Bildung und ForschungNational Institute for Health and Care ResearchCancer Council NSWOvarian Cancer AustraliaPeter MacCallum FoundationMedical Research and Materiel CommandNSW Ministry of HealthCancer Council South AustraliaDeutsches KrebsforschungszentrumOvarian Cancer Research FundCancer AustraliaNational Institutes of Health
KeywordsCD20FOXP3CD68Stromal cellImmune systemCD8MedicineCancer researchTissue microarrayCD3Tumor microenvironmentPathologyImmunohistochemistryOncologyImmunology

Abstract

fetched live from OpenAlex

OBJECTIVE: Mucinous ovarian carcinoma (MOC) is a rare histotype of ovarian cancer, with low response rates to standard chemotherapy, and very poor survival for patients diagnosed at advanced stage. There is a limited understanding of the MOC immune landscape, and consequently whether immune checkpoint inhibitors could be considered for a subset of patients. METHODS: We performed multicolor immunohistochemistry (IHC) and immunofluorescence (IF) on tissue microarrays in a cohort of 126 MOC patients. Cell densities were calculated in the epithelial and stromal components for tumor-associated macrophages (CD68+/PD-L1+, CD68+/PD-L1-), T cells (CD3+/CD8-, CD3+/CD8+), putative T-regulatory cells (Tregs, FOXP3+), B cells (CD20+/CD79A+), plasma cells (CD20-/CD79a+), and PD-L1+ and PD-1+ cells, and compared these values with clinical factors. Univariate and multivariable Cox Proportional Hazards assessed overall survival. Unsupervised k-means clustering identified patient subsets with common patterns of immune cell infiltration. RESULTS: Mean densities of PD1+ cells, PD-L1- macrophages, CD4+ and CD8+ T cells, and FOXP3+ Tregs were higher in the stroma compared to the epithelium. Tumors from advanced (Stage III/IV) MOC had greater epithelial infiltration of PD-L1- macrophages, and fewer PD-L1+ macrophages compared with Stage I/II cancers (p = 0.004 and p = 0.014 respectively). Patients with high epithelial density of FOXP3+ cells, CD8+/FOXP3+ cells, or PD-L1- macrophages, had poorer survival, and high epithelial CD79a + plasma cells conferred better survival, all upon univariate analysis only. Clustering showed that most MOC (86%) had an immune depleted (cold) phenotype, with only a small proportion (11/76,14%) considered immune inflamed (hot) based on T cell and PD-L1 infiltrates. CONCLUSION: In summary, MOCs are mostly immunogenically 'cold', suggesting they may have limited response to current immunotherapies.

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)0.001
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesInsufficient payload (model declined to judge)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.138
Threshold uncertainty score0.997

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
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)0.0040.000

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 head0.021
GPT teacher head0.285
Teacher spread0.263 · 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.

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

Citations26
Published2022
Admission routes2
Has abstractyes

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