Evidence map›Paper›PMID 34555853›Full record

ArticleBlood advances2021

Single-cell polyfunctional proteomics of CD4 cells from patients with AML predicts responses to anti-PD-1-based therapy.

Hussein A Abbas, Zoe Alaniz, Sean Mackay, Matthew Cyr, Jing Zhou, Ghayas C Issa, Mansour Alfayez, Jairo Matthews, Steven M Kornblau, Elias Jabbour and 4 more

Open access · goldAbstract read
In one paragraph

Article in Blood advances, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
2.0field-weighted citation impact, top 11% 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

22 citing papers in PubMed, 29 citations in OpenAlex.

  1. Trial
  2. Trial
  3. Review
  4. Review
  5. Article
  6. Article
  7. Article
  8. ZP4: A novel target for CAR-T cell therapy in triple negative breast cancer.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Article
  9. Article
  10. Article
  11. Article
  12. Review
  13. Review
  14. Review
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. 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

14 authors at 2 institutions in 1 country.

Hussein A AbbasDepartment of Leukemia.ORCID 0000-0003-2946-3562
Zoe AlanizDepartment of Leukemia.ORCID 0000-0002-9424-5417
Sean MackayIsoPlexis Corporation, Branford, CT.
Matthew CyrIsoPlexis Corporation, Branford, CT.
Jing ZhouIsoPlexis Corporation, Branford, CT.
Ghayas C IssaDepartment of Leukemia.ORCID 0000-0002-4339-8683
Mansour AlfayezDepartment of Leukemia.
Jairo MatthewsDepartment of Leukemia.
Steven M KornblauDepartment of Leukemia.
Elias JabbourDepartment of Leukemia.
Guillermo Garcia-ManeroDepartment of Leukemia.
Marina KonoplevaDepartment of Leukemia.ORCID 0000-0002-9347-2212
Michael AndreeffDepartment of Leukemia.ORCID 0000-0002-1144-1958
Naval DaverDepartment of Leukemia.ORCID 0000-0001-7103-373X
IsoPlexis (United States) · USThe University of Texas MD Anderson Cancer Center · US

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Scott Kopetz · 1985 to 2026
$290.8M
University of Texas M.D. Anderson Cancer SPORE-LeukemiaP50CA100632 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI KONOPLEVA, MARINA Y · 2003 to 2023
$43.7M
TRAINING FOR ACADEMIC ONCOLOGY/HEMATOLOGYT32CA009666 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Michael Davies, Courtney DiNardo · 1994 to 2026
$9.8M
NCI NIH HHS P30 CA016672NCI NIH HHS P50 CA100632NCI NIH HHS T32 CA009666
6 · The paper itself

Abstract

Acute myeloid leukemia (AML) remains a difficult disease to treat disease. In a phase 2 clinical trial in patients with relapsed/refractory AML, combining the hypomethylating agent, azacitidine, with the PD-1 checkpoint inhibitor, nivolumab, demonstrated encouraging response rates (33%), median event-free, and overall survival, compared with a historical cohort of contemporary patients treated with azacitidine-based therapies, with an acceptable safety profile. Biomarkers of response are yet to be determined. In this study, we leveraged a multiplexed immune assay to assess the functional states of CD4+ and CD8+ cells at a single-cell level in pretherapy bone marrows in 16 patients with relapsed/refractory AML treated with azacitidine/nivolumab. Effector CD4+ but not CD8+ cells had distinct polyfunctional groups and were associated with responses and better outcomes. Further evaluation of the polyfunctional strength index composition across cell types revealed that interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α) were the major drivers of enhanced polyfunctionality index of pretherapy CD4+ subset, whereas Granzyme B, IFN-γ, MIP-1b, and TNF-α drove the nonsignificantly enhanced pretreatment Polyfunctional Strength Index of CD8+ subset in the responders. Single-cell polyfunctional assays were predictive of response in AML and may have a potential role as a biomarker in the wider sphere of immunotherapy.

Indexed as

Leukemia, Myeloid, AcuteProteomicsAzacitidineCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesHumansAzacitidine

Identifiers

PMID34555853
PMCPMC8759127
OpenAlexW3199315010

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.