Evidence map›Paper›PMID 30285852›Full record

ArticleJournal for immunotherapy of cancer2018

Multidimensional, quantitative assessment of PD-1/PD-L1 expression in patients with Merkel cell carcinoma and association with response to pembrolizumab.

Nicolas A Giraldo, Peter Nguyen, Elizabeth L Engle, Genevieve J Kaunitz, Tricia R Cottrell, Sneha Berry, Benjamin Green, Abha Soni, Jonathan D Cuda, Julie E Stein and 17 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal for immunotherapy of cancer, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 104 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
104citing papers in PubMed, 3 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

104 citing papers in PubMed, 3 syntheses or guidelines pooled it.

  1. Guideline
  2. Pooled it
  3. Anti-PD-1/L1-associated immune-related adverse events as harbinger of favorable clinical outcome: systematic review and meta-analysis.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2021
    Pooled it
  4. Trial
  5. Trial
  6. Neoadjuvant Nivolumab for Patients With Resectable Merkel Cell Carcinoma in the CheckMate 358 Trial.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2020
    Trial
  7. Durable Tumor Regression and Overall Survival in Patients With Advanced Merkel Cell Carcinoma Receiving Pembrolizumab as First-Line Therapy.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2019
    Trial
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Review
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  15. Article
  16. Spatially organized inflammatory myeloid-CD8bioRxiv : the preprint server for biology · 2025
    Article
  17. Article
  18. Article
  19. Article
  20. Review

44 more citing papers are in PubMed but not listed here.

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

27 authors.

Nicolas A GiraldoDepartment of Dermatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Peter NguyenDepartment of Dermatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Elizabeth L EngleDepartment of Oncology, Johns Hopkins University School of Medicine, The Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA.
Genevieve J KaunitzDepartment of Dermatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Tricia R CottrellDepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Sneha BerryDepartment of Oncology, Johns Hopkins University School of Medicine, The Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA.
Benjamin GreenDepartment of Dermatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Abha SoniDepartment of Dermatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Jonathan D CudaDepartment of Dermatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Julie E SteinDepartment of Dermatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Joel C SunshineDepartment of Dermatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Farah SuccariaDepartment of Dermatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Haiying XuDepartment of Dermatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Aleksandra OgurtsovaDepartment of Dermatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Ludmila DanilovaDepartment of Biostatistics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Candice D ChurchDivision of Dermatology, Department of Medicine, University of Washington Medical Center, Seattle, WA, USA.
Natalie J MillerDivision of Dermatology, Department of Medicine, University of Washington Medical Center, Seattle, WA, USA.
Steve FlingCancer Immunotherapy Trials Network, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Lisa LundgrenCancer Immunotherapy Trials Network, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Nirasha RamchurrenDivision of Dermatology, Department of Medicine, University of Washington Medical Center, Seattle, WA, USA.
Jennifer H YearleyMerck Research Laboratories, Kenilworth, NJ, USA.
Evan J LipsonDepartment of Oncology, Johns Hopkins University School of Medicine, The Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA.
Mac CheeverCancer Immunotherapy Trials Network, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Robert A AndersDepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Paul T NghiemDivision of Dermatology, Department of Medicine, University of Washington Medical Center, Seattle, WA, USA.
Suzanne L TopalianDepartment of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Janis M TaubeDepartment of Dermatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. jtaube1@jhmi.edu.ORCID 0000-0002-8273-4395

Funding

Translational Bioimaging Core Shared ResourceP30CA015704 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI Eric Collisson · 1985 to 2026
$296.4M
Translational Research Central ServicesP30CA006973 · NCI · JOHNS HOPKINS UNIVERSITY · PI WILLIAM George NELSON · 1985 to 2026
$208.6M
Understand & overcome resistance to PD-1P01CA225517 · NCI · UNIVERSITY OF WASHINGTON · PI Cecilia C Yeung · 2019 to 2026
$22.7M
Cancer Immunotherapy Trials Network Central Operations and Statistical CenterUM1CA154967 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI DAVIDSON, NANCY ELLEN · 2017 to 2022
$20.7M
PD-1/PD-L1 modulation in cancer therapyR01CA142779 · NCI · JOHNS HOPKINS UNIVERSITY · PI PARDOLL, DREW M., TAUBE, JANIS M · 2010 to 2025
$8.2M
Opportunities for Pathology Trainees in Cancer ResearchT32CA193145 · NCI · JOHNS HOPKINS UNIVERSITY · PI ANDERS, ROBERT A., EBERHART, CHARLES G · 2015 to 2025
$2.6M
Pathogenetic and prognostic studies for improved therapy of Merkel cell carcinomaK24CA139052 · NCI · UNIVERSITY OF WASHINGTON · PI NGHIEM, PAUL · 2009 to 2018
$1.8M
NCI NIH HHS K24 CA139052NCI NIH HHS P01 CA225517NCI NIH HHS P30 CA006973NCI NIH HHS P30 CA015704NCI NIH HHS R01 CA142779NCI NIH HHS T32 CA193145NCI NIH HHS UM1 CA154967
6 · The paper itself

Abstract

backgroundWe recently reported a 56% objective response rate in patients with advanced Merkel cell carcinoma (MCC) receiving pembrolizumab. However, a biomarker predicting clinical response was not identified.

methodsPretreatment FFPE tumor specimens (n = 26) were stained for CD8, PD-L1, and PD-1 by immunohistochemistry/immunofluorescence (IHC/IF), and the density and distribution of positive cells was quantified to determine the associations with anti-PD-1 response. Multiplex IF was used to test a separate cohort of MCC archival specimens (n = 16), to identify cell types expressing PD-1.

resultsTumors from patients who responded to anti-PD-1 showed higher densities of PD-1+ and PD-L1+ cells when compared to non-responders (median cells/mm

conclusionsWhile the binomial presence or absence of PD-L1 expression in the TME was not sufficient to predict response to anti-PD-1 in patients with MCC, we show that quantitative assessments of PD-1+ and PD-L1+ cell densities as well as the geographic interactions between these two cell populations correlate with clinical response. Cell types expressing PD-1 in the TME include CD8+ T-cells, CD4+ T-cells, T

Indexed as

Antibodies, Monoclonal, HumanizedAntineoplastic Agents, ImmunologicalCarcinoma, Merkel CellFemaleHumansMaleProgrammed Cell Death 1 ReceptorAntibodies, Monoclonal, HumanizedAntineoplastic Agents, ImmunologicalpembrolizumabProgrammed Cell Death 1 ReceptorMerkel cellMultispectral immunofluorescencePD-1PD-L1Pembrolizumab

Identifiers

PMID30285852
PMCPMC6167897

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Registered trials

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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.