Evidence map›Paper›PMID 38234786›Full record

ArticlemedRxiv : the preprint server for health sciences2023

Pembrolizumab alters the tumor immune landscape in a patient with dMMR glioblastoma.

Todd Bartkowiak, Asa A Brockman, Bret C Mobley, Hannah Harmsen, Paul Moots, Ryan Merrell, Douglas B Johnson, Reid C Thompson, Vinay K Puduvalli, Rebecca A Ihrie

Open access · greenAbstract readPreprint
In one paragraph

Article in medRxiv : the preprint server for health sciences, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
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

0 citing papers in PubMed, 2 citations in OpenAlex.

No citing paper in PubMed yet.

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.

Todd BartkowiakDepartment of Cell and Developmental Biology, Vanderbilt University, Nashville, TN, USA.
Asa A BrockmanDepartment of Cell and Developmental Biology, Vanderbilt University, Nashville, TN, USA.
Bret C MobleyDepartment of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA.
Hannah HarmsenDepartment of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA.
Paul MootsVanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA.
Ryan MerrellVanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA.
Douglas B JohnsonVanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA.
Reid C ThompsonVanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA.
Vinay K PuduvalliDepartment of Neuro-Oncology, Division of Cancer Medicine, MD Anderson Cancer Center, Houston, TX, USA.
Rebecca A IhrieDepartment of Cell and Developmental Biology, Vanderbilt University, Nashville, TN, USA.ORCID 0000-0003-0439-0141
Vanderbilt University Medical Center · USVanderbilt University · USNeurological Surgery · USThe University of Texas MD Anderson Cancer Center · US

Funding

Tumor Immunology and Microenvironment Research ProgramP30CA068485 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Ben Ho Park · 1995 to 2026
$172.8M
MULTIDISCIPLINARY BASIC RESEARCH TRAINING IN CANCERT32CA009592 · NCI · VANDERBILT UNIVERSITY · PI Justin M Balko, Julie A Rhoades (Sterling) · 1987 to 2026
$10.4M
Identifying mTOR Dependent Periods During Brain DevelopmentR01NS118580 · NINDS · VANDERBILT UNIVERSITY · PI ESS, KEVIN C, IHRIE, REBECCA A · 2020 to 2024
$2.1M
Pannoramic 250 BF Flash Tissue Microarray systemS10OD016355 · OD · VANDERBILT UNIVERSITY · PI BOYD, KELLI L. · 2014 to 2014
$453k
Memory potential, molecular characterization, and translational applications of the novel ThEO/TcEO T cell phenotypeK00CA212447 · NCI · VANDERBILT UNIVERSITY · PI BARTKOWIAK, TODD · 2018 to 2021
$309k
Leica Bond RXS10OD023475 · OD · VANDERBILT UNIVERSITY MEDICAL CENTER · PI BOYD, KELLI L. · 2018 to 2018
$213k
Arcturus XT-TI Laser Capture Microdissection InstrumentIS1BX003154 · VA · VETERANS HEALTH ADMINISTRATION · PI GOLDENRING, JAMES RICHARD · 2015 to 2015
–
BLRD VA IS1 BX003154NCI NIH HHS K00 CA212447NCI NIH HHS P30 CA068485NCI NIH HHS T32 CA009592NIH HHS S10 OD016355NIH HHS S10 OD023475NINDS NIH HHS R01 NS118580
6 · The paper itself

Abstract

Congenital DNA mismatch repair defects (dMMR), such as Lynch Syndrome, predispose patients to a variety of cancers and account for approximately 1% of glioblastoma cases. While few therapeutic options exist for glioblastoma, checkpoint blockade therapy has proven effective in dMMR tumors. Here we present a case study of a male in their 30s diagnosed with dMMR glioblastoma treated with pembrolizumab who experienced a partial response to therapy. Using a multiplex IHC analysis pipeline on archived slide specimens from tumor resections at diagnosis and after therapeutic interventions, we quantified changes in the frequency and spatial distribution of key cell populations in the tumor tissue. Notably, proliferating (KI67+) macrophages and T cells increased in frequency as did other KI67+ cells within the tumor. Therapeutic intervention remodeled the cellular spatial distribution in the tumor leading to a greater frequency of macrophage/tumor cell interactions and T cell/T cell interactions, highlighting impacts of checkpoint blockade on tumor cytoarchitecture and revealing spatial patterns that may indicate advantageous immune interactions in glioma and other solid tumors treated with these agents.

Indexed as

checkpoint blockadeDNA mismatch repair deficiencyglioblastomaimmunohistochemistrymachine learning

Identifiers

PMID38234786
PMCPMC10793510
OpenAlexW4390230333

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.