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119 Uncovering spatial biology of mouse tumor immune microenvironment using imaging mass cytometry

2023· article· en· W4388089028 on OpenAlexaff
Qanber Raza, Liang Lim, Thomas D. Pfister

Bibliographic record

VenueRegular and Young Investigator Award Abstracts · 2023
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicSingle-cell and spatial transcriptomics
Canadian institutionsFluidigm (Canada)Canadian Standards Association
Fundersnot available
KeywordsMass cytometryTumor microenvironmentImmune systemCancer researchContext (archaeology)PathologyMedicineBiologyImmunologyPhenotype

Abstract

fetched live from OpenAlex

<h3>Background</h3> Advances in therapies targeting immuno-oncological processes that dictate tumor growth, metastasis, and immune response require comprehensive preclinical research. Mouse models have proven to be a preferred tool for determining important factors that influence tumor development. Conducting multiparametric analysis on mouse tumor tissue has the potential to significantly expand capabilities of tumor-targeting therapies. Imaging Mass Cytometry™ (IMC™) is a proven high-plex imaging technology that enables deep characterization of the complexity of tumor tissue to capture spatial context while eliminating artifacts caused by spectral overlap and background autofluorescence. The Hyperion™ Imaging System utilizes IMC technology to simultaneously assess 40-plus individual structural and functional markers in tissues. Here, we showcase the Maxpar® OnDemand Mouse Immuno-Oncology IMC Panel Kit (PN 9100005) for application on mouse tumor tissues. <h3>Methods</h3> We compiled a 33-plex Mouse Immuno-Oncology IMC Panel Kit to evaluate immuno-oncological-related processes and applied it to a tissue microarray containing a large variety of mouse tumors including non-small-cell lung cancer, B cell lymphoma, colon adenocarcinoma, and renal carcinoma. We digitized high-plex data from mouse tissues using the Hyperion Imaging System and generated images demonstrating the detailed layout of the tumor immune microenvironment (TIME). We conducted single-cell analysis to identify specific and relevant populations of tumor and immune cells. We further applied neighborhood analysis to determine spatial relationships between selected cellular clusters distributed across the TIME. <h3>Results</h3> The Maxpar OnDemand™ Mouse Immuno-Oncology IMC Panel Kit successfully detected immune cell infiltration and activation, signaling pathway activation, biomarkers of epithelial-to-mesenchymal transition (EMT), metabolic activity, growth, and the tumor tissue architecture. Single-cell analysis of non-small-cell lung carcinoma, B cell lymphoma, colon adenocarcinoma, and renal carcinoma separated distinct cellular clusters representing tumor, immune, stromal, and vascular cells. Neighborhood analysis pinpointed spatial relationships between specific cellular clusters within the TIME. <h3>Conclusions</h3> Our quantitative analysis of tumor composition revealed critical insights regarding prognostic parameters such as metastatic and growth potential of tumor cells and activity of immune cell infiltrates. Overall, this work demonstrates the tumor spatial profiling capabilities of IMC technology and provides evidence of its successful application in mouse tumor models. <h3>Ethics Approval</h3> The samples obtained for this study were sourced from an accredited commercial provider.

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 categoriesMeta-epidemiology (narrow)
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 score0.042
Threshold uncertainty score1.000

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)0.0000.000

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 head0.012
GPT teacher head0.227
Teacher spread0.215 · 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 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

Citations0
Published2023
Admission routes1
Has abstractyes

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