Evidence map›Paper›PMID 36732326›Full record

ArticleBlood cancer journal2023

Circulating Th17 T cells at treatment onset predict autoimmune toxicity of PI3Kδ inhibitors.

Deepti Gadi, Stephen P Martindale, Pui Yan Chiu, Jasneet Khalsa, Pei-Hsuan Chen, Stacey M Fernandes, Zixu Wang, Svitlana Tyekucheva, John-Hanson Machado, David C Fisher and 5 more

Open access · goldAbstract read
In one paragraph

Article in Blood cancer journal, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.6field-weighted citation impact, top 29% 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

3 citing papers in PubMed, 2 citations in OpenAlex.

  1. Article
  2. Review
  3. 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

15 authors at 3 institutions in 1 country.

Deepti Gadi *Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Stephen P Martindale *Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Pui Yan ChiuCenter for Immunology & Inflammation, Institute of Molecular Medicine, The Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY, USA.
Jasneet KhalsaDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Pei-Hsuan ChenCenter for Immuno-Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Stacey M FernandesDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Zixu WangDepartment of Data Sciences, Dana-Farber Cancer Institute, Boston, MA, USA.
Svitlana TyekuchevaDepartment of Data Sciences, Dana-Farber Cancer Institute, Boston, MA, USA.
John-Hanson MachadoDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.ORCID 0000-0003-0477-3476
David C FisherDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Philippe ArmandDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.ORCID 0000-0001-6098-1603
Matthew S DavidsDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.ORCID 0000-0003-4529-2003
Scott RodigCenter for Immuno-Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Barbara SherryCenter for Immunology & Inflammation, Institute of Molecular Medicine, The Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY, USA.ORCID 0000-0003-3119-1463
Jennifer R BrownDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. jennifer_brown@dfci.harvard.edu.ORCID 0000-0003-2040-4961
Harvard University · USDana-Farber Cancer Institute · USNorthwell Health · US

Funding

Unlocking the Potential of PI3K Inhibition in CLLR01CA213442 · NCI · DANA-FARBER CANCER INST · PI BROWN, JENNIFER R · 2017 to 2021
$2.9M
Th17 generation, action and therapeutic relevance in chronic lymphocytic leukemiaR01CA238523 · NCI · FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH · PI CHIORAZZI, NICHOLAS, SHERRY, BARBARA A · 2020 to 2024
$2.7M
NCI NIH HHS R01 CA213442NCI NIH HHS R01 CA238523
6 · The paper itself

Abstract

PI3Kδ inhibitors are approved for the therapy of B cell malignancies, but their clinical use has been limited by unpredictable autoimmune toxicity, despite promising efficacy and evidence that toxicity is associated with improved clinical outcomes. Prior phenotypic evaluation by CyTOF has identified increases in activated CD8 T cells with activation of Th17 T cells, as well as decreases in Tregs, particularly in patients with toxicity. Here we sought to further understand the effects of idelalisib and duvelisib in vitro, and demonstrate that both idelalisib and duvelisib can inhibit T cell proliferation as well as Th1 and Treg differentiation in vitro, while promoting Th2 and Th17 differentiation. We further demonstrate directly using intracellular flow cytometry that autoimmune toxicity in patients is associated with higher absolute numbers of CD4 and CD8 T cells with Th17 differentiation in peripheral blood prior to therapy, and that gastrointestinal tissues from patients with active autoimmune complications of PI3Kδ inhibitors show infiltration with Th17

Indexed as

Th17 CellsT-Lymphocytes, RegulatoryCD8-Positive T-LymphocytesCell DifferentiationFlow CytometryHumans

Identifiers

PMID36732326
PMCPMC9895075
OpenAlexW4319036846

What OpenQuestion holds

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LicenceCC BY
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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.