Evidence map›Paper›PMID 33504554›Full record

ArticleClinical cancer research : an official journal of the American Association for Cancer Research2021

Biomarker Discovery in Patients with Immunotherapy-Treated Melanoma with Imaging Mass Cytometry.

Sandra Martinez-Morilla, Franz Villarroel-Espindola, Pok Fai Wong, Maria I Toki, Thazin Nwe Aung, Vasiliki Pelekanou, Brian Bourke-Martin, Kurt A Schalper, Harriet M Kluger, David L Rimm

Abstract read
In one paragraph

Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
43citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

43 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Guideline
  2. Review
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  5. International journal of molecular sciences · 2025
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  16. Immune Cytolytic Activity and Strategies for Therapeutic Treatment.International journal of molecular sciences · 2024
    Review
  17. Article
  18. OPTIMAL: An OPTimized Imaging Mass cytometry AnaLysis framework for benchmarking segmentation and data exploration.Cytometry. Part A : the journal of the International Society for Analytical Cytology · 2024
    Article
  19. Review
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Sandra Martinez-MorillaDepartment of Pathology, Yale School of Medicine, New Haven, Connecticut.
Franz Villarroel-EspindolaDepartment of Pathology, Yale School of Medicine, New Haven, Connecticut.
Pok Fai WongDepartment of Pathology, Yale School of Medicine, New Haven, Connecticut.
Maria I TokiDepartment of Pathology, Yale School of Medicine, New Haven, Connecticut.
Thazin Nwe AungDepartment of Pathology, Yale School of Medicine, New Haven, Connecticut.ORCID 0000-0003-4150-0426
Vasiliki PelekanouDepartment of Pathology, Yale School of Medicine, New Haven, Connecticut.ORCID 0000-0002-8431-1927
Brian Bourke-MartinNavigate BioPharma Services, Inc., Carlsbad, California.
Kurt A SchalperDepartment of Pathology, Yale School of Medicine, New Haven, Connecticut.
Harriet M KlugerSection of Medical Oncology, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut.
David L RimmDepartment of Pathology, Yale School of Medicine, New Haven, Connecticut. david.rimm@yale.edu.ORCID 0000-0001-5820-4397

Funding

Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9M
Yale Pathology Tissue Services Shared ResourceP30CA016359 · NCI · YALE UNIVERSITY · PI DAVID L RIMM · 1985 to 2026
$85.0M
Yale SPORE in Skin CancerP50CA121974 · NCI · YALE UNIVERSITY · PI DAVID F STERN · 2006 to 2026
$43.9M
Yale SPORE in Lung Cancer (YSILC): The Biology and Personalized Treatment of Lung CancerP50CA196530 · NCI · YALE UNIVERSITY · PI Shuangge Ma · 2015 to 2026
$31.1M
NCATS NIH HHS UL1 TR001863NCI NIH HHS P30 CA016359NCI NIH HHS P50 CA121974NCI NIH HHS P50 CA196530
6 · The paper itself

Abstract

purposeImaging mass cytometry (IMC) is among the first tools with the capacity for multiplex analysis of more than 40 targets, which provides a novel approach to biomarker discovery. Here, we used IMC to characterize the tumor microenvironment of patients with metastatic melanoma who received immunotherapy in efforts to find indicative factors of treatment response. In spite of the new power of IMC, the image analysis aspects are still limited by the challenges of cell segmentation. EXPERIMENTAL

designHere, rather than segment, we performed image analysis using a newly designed version of the AQUA software to measure marker intensity in molecularly defined compartments: tumor cells, stroma, T cells, B cells, and macrophages. IMC data were compared with quantitative immunofluorescence (QIF) and digital spatial profiling.

resultsValidation of IMC results for immune markers was confirmed by regression with additional multiplexing methods and outcome assessment. Multivariable analyses by each compartment revealed significant associations of 12 markers for progression-free survival and seven markers for overall survival (OS). The most compelling indicative biomarker, beta2-microglobulin (B2M), was confirmed by correlation with OS by QIF in the discovery cohort and validated in an independent published cohort profiled by mRNA expression.

conclusionsUsing digital image analysis based on pixel colocalization to assess IMC data allowed us to quantitively measure 25 markers simultaneously on formalin-fixed, paraffin-embedded tissue microarray samples. In addition to showing high concordance with other multiplexing technologies, we identified a series of potentially indicative biomarkers for immunotherapy in metastatic melanoma, including B2M.

Indexed as

Tumor Microenvironmentbeta 2-MicroglobulinBiomarkers, TumorHumansImage CytometryImmune Checkpoint InhibitorsMelanomaRNA, MessengerTissue Array AnalysisB2M protein, humanbeta 2-MicroglobulinBiomarkers, TumorImmune Checkpoint InhibitorsRNA, Messenger

Identifiers

PMID33504554
PMCPMC8026677

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.