Evidence map›Paper›PMID 34780566›Full record

ArticlePloS one2021

PD-L1 expression on circulating tumor cells and platelets in patients with metastatic breast cancer.

Elizabeth P Darga, Emily M Dolce, Fang Fang, Kelley M Kidwell, Christina L Gersch, Steven Kregel, Dafydd G Thomas, Anoop Gill, Martha E Brown, Steven Gross and 6 more

Registry-linked trialOpen access · goldAbstract read
In one paragraph

Article in PloS one, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05810402 (Liver Cancer and Immunotherapy), which is not on this map. Cited by 37 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed, 1 pooled it
3.8field-weighted citation impact, top 4% of its field
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.

NCT05810402 narecruitingnot on this mapstarted 2023, after this paper: background citation

Liver Cancer and Immunotherapy : Clinical Relevance of LIquid BioPSY

TypeinterventionalSponsorUniversity Hospital, MontpellierRan2023 to 2027Enrolled60ConditionsHepatocellular Carcinoma, BCLC Stage B Hepatocellular Carcinoma, BCLC Stage C Hepatocellular Carcinoma, Immune Checkpoint InhibitorArmsLiquid Biopsy
3 · Its place in the literature

Who cites it

37 citing papers in PubMed, 1 synthesis or guideline pooled it, 53 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Review
  4. Review
  5. CTC cluster in breast cancer: synergetic metastasis promotion mechanism and transformation path from platelet cloaking to leukocyte escort.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
    Review
  6. Observational
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  8. Review
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  11. Circulating biomarkers for diagnosis and response to therapies in cancer patients.International review of cell and molecular biology · 2025
    Review
  12. Article
  13. Review
  14. Radiolabelling and preclinical characterisation of [European journal of nuclear medicine and molecular imaging · 2024
    Article
  15. Article
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  18. Article
  19. Article
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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

16 authors at 2 institutions in 1 country.

Elizabeth P DargaBreast Oncology Program, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, United States of America.
Emily M DolceBreast Oncology Program, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, United States of America.ORCID 0000-0001-7212-8116
Fang FangDepartment of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, Michigan, United States of America.
Kelley M KidwellUniversity of Michigan Rogel Cancer Center, University of Michigan, Ann Arbor, Michigan, United States of America.ORCID 0000-0002-1717-4483
Christina L GerschBreast Oncology Program, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, United States of America.
Steven KregelUniversity of Michigan Rogel Cancer Center, University of Michigan, Ann Arbor, Michigan, United States of America.
Dafydd G ThomasUniversity of Michigan Rogel Cancer Center, University of Michigan, Ann Arbor, Michigan, United States of America.
Anoop GillBreast Oncology Program, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, United States of America.
Martha E BrownBreast Oncology Program, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, United States of America.
Steven GrossMenarini Silicon Biosystems, Huntingdon Valley, Pennsylvania, United States of America.
Mark ConnellyMenarini Silicon Biosystems, Huntingdon Valley, Pennsylvania, United States of America.
Michael HolinstatDepartments of Pharmacology and Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, United States of America.ORCID 0000-0001-5100-1933
Erin F CobainBreast Oncology Program, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, United States of America.
James M RaeBreast Oncology Program, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, United States of America.
Daniel F HayesBreast Oncology Program, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, United States of America.
Costanza PaolettiBreast Oncology Program, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, United States of America.
University of Michigan · USSilicon Labs (United States) · US

Funding

XenograftP30CA046592 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI THEODORE S LAWRENCE · 1988 to 2026
$178.2M
NCI NIH HHS P30 CA046592
6 · The paper itself

Abstract

backgroundImmune checkpoint inhibition is effective in several cancers. Expression of programmed death-ligand 1 (PD-L1) on circulating tumor or immune effector cells could provide insights into selection of patients for immune checkpoint inhibition.

methodsWhole blood was collected at serial timepoints from metastatic breast cancer patients and healthy donors for circulating tumor cell (CTC) and platelet PD-L1 analysis with a phycoerythrin-labeled anti-human PD-L1 monoclonal antibody (Biolegend clone 29E.2A3) using the CellSearch® assay. CTC PD-L1 was considered positive if detected on at least 1% of the cells; platelet PD-L1 was considered positive if ≥100 platelets per CellSearch frame expressed PD-L1.

resultsA total of 207 specimens from 124 metastatic breast cancer patients were collected. 52/124 (42%) samples at timepoint-1 (at or close to time of progressive disease) had ≥5 CTC/7.5ml whole blood. Of those, 21 (40%) had positive CTC PD-L1. In addition, platelet PD-L1 expression was observed in 35/124 (28%) at timepoint-1. Platelet PD-L1 was not detected in more than 70 specimens from 12 healthy donors. Platelet PD-L1 was associated with ≥5 CTC/7.5ml whole blood (p = 0.0002), less likely in patients with higher red blood cell counts (OR = 0.72, p<0.001) and a history of smoking tobacco (OR = 0.76, p<0.001). Platelet PD-L1 staining was not associated with tumor marker status, recent procedures or treatments, platelet-affecting drugs, or CTC PD-L1 expression.

conclusionPD-L1 expression was found in metastatic breast cancer patients on both CTC and platelets in an independent fashion. Inter-patient platelet PD-L1 expression was highly heterogeneous suggesting that it is a biological event associated with cancer in some but not all patients. Taken together, our data suggest that CTC and platelet PD-L1 expression could play a role in predicting which patients should receive immune checkpoint inhibition and as a pharmacodynamics biomarker during treatment.

Indexed as

Up-RegulationB7-H1 AntigenBlood PlateletsBreast NeoplasmsCase-Control StudiesCell Line, TumorFemaleGene Expression Regulation, NeoplasticGene Knockdown TechniquesHumansMCF-7 CellsNeoplasm MetastasisNeoplastic Cells, CirculatingB7-H1 AntigenCD274 protein, human

Identifiers

PMID34780566
PMCPMC8592410
OpenAlexW3129118764

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Registered trials

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.