Evidence map›Paper›PMID 34337428›Full record

ArticleAging and cancer2020

Impact of age-related T cell dynamics on the identification of biomarkers predictive of immunotherapy discontinuation: a prospective cohort study.

Jason E Galloway, Andrea M Holderbaum, Namrata Arya, Suohui Zhang, Michael S Bodnar, Ruthann Norman, William E Carson, Lianbo Yu, Kari L Kendra, Christin E Burd

Open access · goldAbstract read
In one paragraph

Article in Aging and cancer, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.1field-weighted citation impact, top 52% 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.

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

2 citing papers in PubMed, 1 citations in OpenAlex.

  1. Article
  2. Peripheral blood CD3British journal of haematology · 2022
    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

10 authors at 2 institutions in 1 country.

Jason E GallowayDepartment of Molecular Genetics, The Ohio State University College of Arts and Sciences, Columbus, OH 43210.
Andrea M HolderbaumDepartment of Molecular Genetics, The Ohio State University College of Arts and Sciences, Columbus, OH 43210.
Namrata AryaDepartment of Molecular Genetics, The Ohio State University College of Arts and Sciences, Columbus, OH 43210.
Suohui ZhangDepartment of Molecular Genetics, The Ohio State University College of Arts and Sciences, Columbus, OH 43210.
Michael S BodnarDepartment of Molecular Genetics, The Ohio State University College of Arts and Sciences, Columbus, OH 43210.
Ruthann NormanDepartment of Surgery, Division of Surgical Oncology, The Ohio State University College of Medicine, Columbus, OH 43210.
William E CarsonDepartment of Surgery, Division of Surgical Oncology, The Ohio State University College of Medicine, Columbus, OH 43210.
Lianbo YuCenter for Biostatistics, Department of Biomedical Informatics, The Ohio State University College of Medicine, Columbus, OH 43210.
Kari L KendraMedical Oncology Division, Department of Internal Medicine, The Ohio State University College of Medicine, Columbus, OH 43210.
Christin E BurdDepartment of Molecular Genetics, The Ohio State University College of Arts and Sciences, Columbus, OH 43210.
The Ohio State University · USFlorida State University · US

Funding

Translational Therapeutics Research Program (TT)P30CA016058 · NCI · OHIO STATE UNIVERSITY · PI Tasleem J Padamsee · 1985 to 2026
$132.3M
The OSU Center for Clinical and Translational Science: Advancing Today's Discoveries to Improve HealthUL1TR002733 · NCATS · OHIO STATE UNIVERSITY · PI RINGEL, MATTHEW D · 2018 to 2022
$28.9M
Marital quality and longevity: Biobehavioral pathwaysR01AG057032 · NIA · OHIO STATE UNIVERSITY · PI KIECOLT-GLASER, JANICE · 2017 to 2021
$3.2M
Impact of senescence on T-cell function and immunotherapeutic responseR01AG059711 · NIA · OHIO STATE UNIVERSITY · PI BURD, CHRISTIN E · 2018 to 2022
$2.1M
NCATS NIH HHS UL1 TR002733NCI NIH HHS P30 CA016058NIA NIH HHS R01 AG057032NIA NIH HHS R01 AG059711
6 · The paper itself

Abstract

backgroundThe impact of biologic aging on immune checkpoint inhibitor (ICI) toxicity and efficacy is underexplored in metastatic melanoma (MM). In peripheral blood T-lymphocytes (PBTLs), biologic aging is characterized by changes in T-cell composition and cellular senescence. Whether indicators of PBTL biologic aging vary in MM patients or can be used to predict premature ICI discontinuation (pID) is unknown.

methodsWe prospectively collected PBTLs from 117 cancer-free controls and 46 MM patients scheduled to begin pembrolizumab or nivolumab monotherapy. 74 mRNAs indicative of T-cell subsets, activation, co-stimuation/inhibition and cellular senescence were measured by Nanostring. Relationships between each mRNA and chronologic age were assessed in patients and controls. Candidate biomarkers were identified by calculating the hazard ratio (HR) for pID in patients divided into low and high groups based on log-transformed mRNA levels or the magnitude by which each mRNA measurement deviated from the control trend (Δage). Area under the curve (AUC) analyses explored the ability of each biomarker to discriminate between patients with and without pID at 6 months and 1 year.

resultsFifteen mRNAs correlated with chronologic age in controls, including markers of T-cell subsets, differentiation, cytokine production and co-stimulation/inhibition. None of these mRNAs remained correlated with age in patients. Median follow-up was 94.8 (1.6-195.7) weeks and 35 of 46 patients discontinued therapy (23 progression, 7 toxicity, 5 comorbidity/patient preference). Elevated pre-therapy

conclusionsCorrelations between transcriptional markers of PBTL composition and chronologic age are disrupted in MM. Correcting for normal, age-related trends in biomarker expression unveils new biomarker candidates predictive of ICI outcomes.

Indexed as

agingAging biomarkeranti-PD-1biomarkerCD27checkpoint inhibitormelanomasenescenceT cell

Identifiers

PMID34337428
PMCPMC8323507
OpenAlexW3109992969

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

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.