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Record W4220913055 · doi:10.1126/sciimmunol.abi5072

Spatially mapping the immune landscape of melanoma using imaging mass cytometry

2022· article· en· W4220913055 on OpenAlexafffund
Dan Moldoveanu, LeeAnn Ramsay, Mathieu Lajoie, Luke Anderson-Trocmé, Marine Lingrand, Diana Berry, Lucas J. M. Perus, Yuhong Wei, Cleber Moraes, Rached Alkallas, Shivshankari Rajkumar, Dongmei Zuo, Matthew Dankner, Eric Hongbo Xu, Nicholas Bertos, Hamed S. Najafabadi, Simon Gravel, Santiago Costantino, Martin J. Richer, Amanda W. Lund, Sonia V. del Rincón, Alan Spatz, Wilson H. Miller, Rahima Jamal, Réjean Lapointe, Anne‐Marie Mes‐Masson, Simon Turcotte, Kevin Petrecca, Sinziana Dumitra, Ari N. Meguerditchian, Keith Richardson, Francine Tremblay, Béatrice Wang, May Chergui, Marie‐Christine Guiot, Kevin Watters, John Stagg, Daniela F. Quail, Catalin Mihalcioiu, Sarkis Meterissian, Ian R. Watson

Bibliographic record

VenueScience Immunology · 2022
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicSingle-cell and spatial transcriptomics
Canadian institutionsMontreal Neurological Institute and HospitalUniversité de MontréalHôpital Maisonneuve-RosemontMcGill Genome CentreCentre Hospitalier de l’Université de MontréalMcGill UniversityMcGill University Health CentreJewish General HospitalMontreal General Hospital
FundersCanadian Institutes of Health Research
KeywordsMass cytometryTumor microenvironmentImmune systemStromal cellCytotoxic T cellMelanomaBiologyCancer researchCD8ImmunotherapyImmunologyImmune checkpointAntigenTumor-infiltrating lymphocytesPhenotype

Abstract

fetched live from OpenAlex

Melanoma is an immunogenic cancer with a high response rate to immune checkpoint inhibitors (ICIs). It harbors a high mutation burden compared with other cancers and, as a result, has abundant tumor-infiltrating lymphocytes (TILs) within its microenvironment. However, understanding the complex interplay between the stroma, tumor cells, and distinct TIL subsets remains a substantial challenge in immune oncology. To properly study this interplay, quantifying spatial relationships of multiple cell types within the tumor microenvironment is crucial. To address this, we used cytometry time-of-flight (CyTOF) imaging mass cytometry (IMC) to simultaneously quantify the expression of 35 protein markers, characterizing the microenvironment of 5 benign nevi and 67 melanomas. We profiled more than 220,000 individual cells to identify melanoma, lymphocyte subsets, macrophage/monocyte, and stromal cell populations, allowing for in-depth spatial quantification of the melanoma microenvironment. We found that within pretreatment melanomas, the abundance of proliferating antigen-experienced cytotoxic T cells (CD8 + CD45RO + Ki67 + ) and the proximity of antigen-experienced cytotoxic T cells to melanoma cells were associated with positive response to ICIs. Our study highlights the potential of multiplexed single-cell technology to quantify spatial cell-cell interactions within the tumor microenvironment to understand immune therapy responses.

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: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.001
Threshold uncertainty score0.002

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.000
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 head0.018
GPT teacher head0.234
Teacher spread0.216 · 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

Citations131
Published2022
Admission routes2
Has abstractyes

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