Evidence map›Paper›PMID 28972595›Full record

ArticleLeukemia2018

Ibrutinib modulates the immunosuppressive CLL microenvironment through STAT3-mediated suppression of regulatory B-cell function and inhibition of the PD-1/PD-L1 pathway.

K Kondo, H Shaim, P A Thompson, J A Burger, M Keating, Z Estrov, D Harris, E Kim, A Ferrajoli, M Daher and 11 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Leukemia, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 papers.

0numbers the graph read from it
0cells of the map it votes in
89citing papers in PubMed
9.1field-weighted citation impact, top 2% 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

89 citing papers in PubMed, 121 citations in OpenAlex.

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29 more citing papers are in PubMed but not listed here.

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

21 authors at 1 institution in 1 country.

K KondoDepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
H ShaimDepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
P A ThompsonDepartment of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
J A BurgerDepartment of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
M KeatingDepartment of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Z EstrovDepartment of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
D HarrisDepartment of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
E KimDepartment of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
A FerrajoliDepartment of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
M DaherDepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
R BasarDepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
M MuftuogluDepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
N ImahashiDepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
A AlsulimanDepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
C SobieskiDepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
E GokdemirDepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
W WierdaDepartment of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
N JainDepartment of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
E LiuDepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
E J ShpallDepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
K RezvaniDepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
The 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
Tissue CoreP01CA081534 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI KIPPS, THOMAS J · 2000 to 2016
$59.5M
NCI NIH HHS P01 CA081534NCI NIH HHS P30 CA016672
6 · The paper itself

Abstract

Ibrutinib, a covalent inhibitor of Bruton Tyrosine Kinase (BTK), is approved for treatment of patients with relapsed/refractory or treatment-naïve chronic lymphocytic leukemia (CLL). Besides directly inhibiting BTK, ibrutinib possesses immunomodulatory properties through targeting multiple signaling pathways. Understanding how this ancillary property of ibrutinib modifies the CLL microenvironment is crucial for further exploration of immune responses in this disease and devising future combination therapies. Here, we investigated the mechanisms underlying the immunomodulatory properties of ibrutinib. In peripheral blood samples collected prospectively from CLL patients treated with ibrutinib monotherapy, we observed selective and durable downregulation of PD-L1 on CLL cells by 3 months post-treatment. Further analysis showed that this effect was mediated through inhibition of the constitutively active signal transducer and activator of transcription 3 (STAT3) in CLL cells. Similar downregulation of PD-1 was observed in CD4+ and CD8+ T cells. We also demonstrated reduced interleukin (IL)-10 production by CLL cells in patients receiving ibrutinib, which was also linked to suppression of STAT3 phosphorylation. Taken together, these findings provide a mechanistic basis for immunomodulation by ibrutinib through inhibition of the STAT3 pathway, critical in inducing and sustaining tumor immune tolerance. The data also merit testing of combination treatments combining ibrutinib with agents capable of augmenting its immunomodulatory effects.

Indexed as

AdenineAgedB7-H1 AntigenB-Lymphocytes, RegulatoryCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesFemaleHumansImmune ToleranceImmunosuppressive AgentsLeukemia, Lymphocytic, Chronic, B-CellMaleMiddle AgedPiperidinesProgrammed Cell Death 1 ReceptorProtein Kinase InhibitorsAdenineB7-H1 AntigenCD274 protein, humanibrutinibImmunosuppressive AgentsPDCD1 protein, humanPiperidinesProgrammed Cell Death 1 ReceptorProtein Kinase InhibitorsProtein-Tyrosine KinasesPyrazolesPyrimidinesSTAT3 protein, humanSTAT3 Transcription Factor

Identifiers

PMID28972595
PMCPMC6128536
OpenAlexW2763953131

What OpenQuestion holds

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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.