Evidence map›Paper›PMID 41008842›Full record

ArticleCancers2025

Mechanistic Insights into Proglumide's Role in Immune Cell Efficacy and Response to Immune Checkpoint Inhibitor Therapy in Hepatocellular Carcinoma.

Priyanka S Doneparthi, Hong Cao, Wenqiang Chen, Wenyu Dou, Hong-Bin Fang, Jill P Smith

Abstract read
In one paragraph

Article in Cancers, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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

6 authors.

Priyanka S DoneparthiDepartment of Oncology, Georgetown University, Washington, DC 20007, USA.
Hong CaoDepartment of Medicine, Georgetown University, Washington, DC 20007, USA.
Wenqiang ChenDepartment of Medicine, Georgetown University, Washington, DC 20007, USA.
Wenyu DouDepartment of Biostatistics, Georgetown University, Washington, DC 20007, USA.
Hong-Bin FangDepartment of Biostatistics, Georgetown University, Washington, DC 20007, USA.ORCID 0000-0002-6173-9082
Jill P SmithDepartment of Oncology, Georgetown University, Washington, DC 20007, USA.ORCID 0000-0002-0835-4802

Funding

Vaccine FacilityP30CA016087 · NCI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI MARK Reid PHILIPS · 1985 to 2026
$83.1M
Tissue Culture Shared ResourceP30CA051008 · NCI · GEORGETOWN UNIVERSITY · PI MARCUS S NOEL · 1990 to 2026
$71.5M
NCI NIH HHS CA051008NCI NIH HHS P30 CA016087NCI NIH HHS P30 CA051008United States Department of Defense CA200380
6 · The paper itself

Abstract

backgroundNew strategies are needed to improve the response to immune checkpoint inhibitors for the treatment of hepatocellular carcinoma.

methodsMice bearing HCC tumors were treated with PBS (control), a PD-1 antibody (PD-1Ab), proglumide, or the combination of proglumide and the PD-1Ab. The tumor microenvironment (TME) was evaluated histologically for fibrosis and by immunohistochemistry for immune cells. To investigate the mechanisms involved in T-cell efficiency, mouse spleen cells were isolated and examined for T-cell exhaustion markers and cytokine release. The mouse microbiome was analyzed using whole-genome sequencing before therapy and at the end of the study.

resultsThe combination of proglumide with a PD-1Ab decreased tumoral fibrosis better than monotherapy, and altered the immune cell signature in the TME by decreasing M2-polarized macrophages and increasing the influx of CD8+ T-cells. Proglumide monotherapy or in combination with the PD-1Ab decreased T-cell exhaustion markers and improved cytokine release. The combination therapy resulted in changes to the microbiome, including increased beneficial bacteria and genera known to enhance the efficacy of ICIs.

conclusionsCo-administration of proglumide with ICIs resulted in remodeling of the TME, changing a "cold" tumor to a "hot" immune-responsive tumor, activating T-cells, and altering the host microbiome to a population of bacteria that are beneficial.

Indexed as

hepatocellular carcinomaimmune checkpoint inhibitorsmicrobiomeT-cellstumor microenvironment

Identifiers

PMID41008842
PMCPMC12468770

What OpenQuestion holds

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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.