Evidence map›Paper›PMID 33261003›Full record

ArticleInternational journal of molecular sciences2020

Exploring the Potential Use of a PBMC-Based Functional Assay to Identify Predictive Biomarkers for Anti-PD-1 Immunotherapy.

Silvia M Bacot, Taylor A Harper, Rebecca L Matthews, Christie Jane Fennell, Adovi Akue, Mark A KuKuruga, Shiowjen Lee, Tao Wang, Gerald M Feldman

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in International journal of molecular sciences, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
–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

15 citing papers in PubMed.

  1. Trial
  2. Review
  3. Article
  4. Circulating PD-1Frontiers in immunology · 2025
    Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Review
  10. Article
  11. Article
  12. Article
  13. Review
  14. Article
  15. Article
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

9 authors.

Silvia M BacotOffice of Biotechnology Products, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD 20993, USA.
Taylor A HarperOffice of Biotechnology Products, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD 20993, USA.ORCID 0000-0002-6088-1028
Rebecca L MatthewsOffice of Biotechnology Products, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD 20993, USA.ORCID 0000-0001-7420-9374
Christie Jane FennellOffice of Biotechnology Products, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD 20993, USA.
Adovi AkueOffice of Vaccines Research & Review, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD 20993, USA.
Mark A KuKurugaOffice of Vaccines Research & Review, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD 20993, USA.
Shiowjen LeeOffice of Biostatistics and Epidemiology, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD 20993, USA.
Tao WangOffice of Biotechnology Products, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD 20993, USA.ORCID 0000-0002-1153-3430
Gerald M FeldmanOffice of Biotechnology Products, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD 20993, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The absence of reliable, robust, and non-invasive biomarkers for anti- Programmed cell death protein 1 (PD-1) immunotherapy is an urgent unmet medical need for the treatment of cancer patients. No predictive biomarkers have been established based on the direct assessment of T cell functions, the primary mechanism of action of anti-PD-1 therapy. In this study, we established a model system to test T cell functions modulated by Nivolumab using anti-CD3 monoclonal antibody (mAb)-stimulated peripheral blood mononuclear cells (PBMCs), and characterized T cell functions primarily based on the knowledge gained from retrospective observations of patients treated with anti-PD-1 immunotherapy. During a comprehensive cytokine profile assessment to identify potential biomarkers, we found that Nivolumab increases expression of T helper type 1 (Th1) associated cytokines such as interferon-γ (IFN-γ) and interleukin-2 (IL-2) in a subset of donors. Furthermore, Nivolumab increases production of Th2, Th9, and Th17 associated cytokines, as well as many proinflammatory cytokines such as IL-6 in a subset of donors. Conversely, Nivolumab treatment has no impact on T cell proliferation, expression of CD25, CD69, or Granzyme B, and only modestly increases in the expansion of regulatory T cells. Our results suggest that assessment of cytokine production using a simple PBMC-based T cell functional assay could be used as a potential predictive marker for anti-PD-1 immunotherapy.

Indexed as

ImmunoassayImmunotherapyAntigens, CDBiomarkersCell ProliferationCytokinesGranzymesHumansLeukocytes, MononuclearLymphocyte ActivationNivolumabProgrammed Cell Death 1 ReceptorTh1 CellsTissue DonorsT-Lymphocytes, RegulatoryAntigens, CDBiomarkersCytokinesGranzymesNivolumabProgrammed Cell Death 1 ReceptorbiomarkercytokinesNivolumabperipheral blood mononuclear cellsT cells

Identifiers

PMID33261003
PMCPMC7730837

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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.