Evidence map›Paper›PMID 37491734›Full record

ReviewImmunological reviews2023

CD4 T cells and toxicity from immune checkpoint blockade.

Noah Earland, Wubing Zhang, Abul Usmani, Aishwarya Nene, Antonella Bacchiocchi, David Y Chen, Mario Sznol, Ruth Halaban, Aadel A Chaudhuri, Aaron M Newman

Open access · greenAbstract readReview
In one paragraph

Review in Immunological reviews, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed, 1 pooled it
3.7field-weighted citation impact, top 6% 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

12 citing papers in PubMed, 1 synthesis or guideline pooled it, 16 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. Article
  5. Article
  6. Review
  7. Review
  8. Article
  9. Article
  10. Review
  11. Deciphering CD4Molecular carcinogenesis · 2024
    Review
  12. 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 at 4 institutions in 1 country.

Noah EarlandDivision of Cancer Biology, Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri, USA.ORCID 0000-0003-0170-407X
Wubing ZhangInstitute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, California, USA.ORCID 0000-0003-2233-299X
Abul UsmaniDivision of Cancer Biology, Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri, USA.ORCID 0000-0001-5485-7323
Aishwarya NeneYale School of Medicine, New Haven, Connecticut, USA.ORCID 0000-0002-5160-5080
Antonella BacchiocchiYale Cancer Center, Yale University School of Medicine, New Haven, Connecticut, USA.
David Y ChenDivision of Dermatology, Washington University School of Medicine, St. Louis, Missouri, USA.ORCID 0000-0002-3681-6576
Mario SznolYale Cancer Center, Yale University School of Medicine, New Haven, Connecticut, USA.ORCID 0000-0003-4137-9662
Ruth HalabanYale Cancer Center, Yale University School of Medicine, New Haven, Connecticut, USA.ORCID 0000-0001-8451-1964
Aadel A ChaudhuriDivision of Cancer Biology, Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri, USA.ORCID 0000-0003-3115-3061
Aaron M NewmanInstitute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, California, USA.ORCID 0000-0002-1857-8172
Washington University in St. Louis · USYale Cancer Center · USCalifornia Institute for Regenerative Medicine · USYale University · US

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
Short-Term Reserch Training: Students in Health SchoolsT35HL007649 · NHLBI · YALE UNIVERSITY · PI Sarwat I Chaudhry, Erica L Herzog · 1987 to 2026
$5.7M
Epigenetic Regulation of Cutaneous TumorigenesisK08CA237727 · NCI · WASHINGTON UNIVERSITY · PI CHEN, DAVID · 2020 to 2024
$1.2M
Ultrasensitive Quantitation of Circulating Tumor DNAR00CA187192 · NCI · STANFORD UNIVERSITY · PI NEWMAN, AARON M · 2017 to 2019
$747k
Integrative genomic biomarkers for predicting response to immunotherapy in melanoma patientsR21CA218950 · NCI · YALE UNIVERSITY · PI HALABAN, RUTH · 2017 to 2018
$401k
NCATS NIH HHS UL1 TR001863NCI NIH HHS K08 CA237727NCI NIH HHS R00 CA187192NCI NIH HHS R21 CA218950NHLBI NIH HHS T35 HL007649
6 · The paper itself

Abstract

Immune-related toxicities, otherwise known as immune-related adverse events (irAEs), occur in a substantial fraction of cancer patients treated with immune checkpoint inhibitors (ICIs). Ranging from asymptomatic to life-threatening, ICI-induced irAEs can result in hospital admission, high-dose corticosteroid treatment, ICI discontinuation, and in some cases, death. A deeper understanding of the factors underpinning severe irAE development will be essential for improved irAE prediction and prevention, toward maximizing the benefits and safety profiles of ICIs. In recent work, we applied mass cytometry, single-cell RNA sequencing, single-cell V(D)J sequencing, bulk RNA sequencing, and bulk T-cell receptor (TCR) sequencing to identify pretreatment determinants of severe irAE development in patients with advanced melanoma. Across 71 patients separated into three cohorts, we found that two baseline features in circulation-elevated activated CD4 effector memory T-cell abundance and TCR diversity-are associated with severe irAE development, independent of the affected organ system within 3 months of ICI treatment initiation. Here, we provide an extended perspective on this work, synthesize and discuss related literature, and summarize practical considerations for clinical translation. Collectively, these findings lay a foundation for data-driven and mechanistic insights into irAE development, with the potential to reduce ICI morbidity and mortality in the future.

Indexed as

Antineoplastic Agents, ImmunologicalNeoplasmsCD4-Positive T-LymphocytesHumansImmune Checkpoint InhibitorsAntineoplastic Agents, ImmunologicalImmune Checkpoint Inhibitorsimmune checkpoint inhibitorsimmune-related adverse eventsimmunotherapyirAEsmelanomapredictive biomarkers

Identifiers

PMID37491734
PMCPMC10838135
OpenAlexW4385264187

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.