Evidence map›Paper›PMID 38429349›Full record

ArticleScientific reports2024

Reversing immunosuppression in the tumor microenvironment of fibrolamellar carcinoma via PD-1 and IL-10 blockade.

S K Daniel, K M Sullivan, L K Dickerson, R J E van den Bijgaart, A F Utria, K P Labadie, H L Kenerson, X Jiang, K S Smythe, J S Campbell and 7 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Scientific reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
2.3field-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

9 citing papers in PubMed, 8 citations in OpenAlex.

  1. Engineering an arginine-nitric oxide circuit inTranslational cancer research · 2026
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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

17 authors at 2 institutions in 1 country.

S K Daniel *Department of Surgery, University of Washington School of Medicine, 1959 NE Pacific Street, Box 356410, Seattle, WA, 98195, USA.
K M Sullivan *Department of Surgery, University of Washington School of Medicine, 1959 NE Pacific Street, Box 356410, Seattle, WA, 98195, USA.
L K DickersonDepartment of Surgery, University of Washington School of Medicine, 1959 NE Pacific Street, Box 356410, Seattle, WA, 98195, USA.
R J E van den BijgaartPublic Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
A F UtriaDepartment of Surgery, University of Washington School of Medicine, 1959 NE Pacific Street, Box 356410, Seattle, WA, 98195, USA.
K P LabadieDepartment of Surgery, University of Washington School of Medicine, 1959 NE Pacific Street, Box 356410, Seattle, WA, 98195, USA.
H L KenersonDepartment of Surgery, University of Washington School of Medicine, 1959 NE Pacific Street, Box 356410, Seattle, WA, 98195, USA.
X JiangDepartment of Surgery, University of Washington School of Medicine, 1959 NE Pacific Street, Box 356410, Seattle, WA, 98195, USA.
K S SmythePublic Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
J S CampbellPublic Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
R H PiercePublic Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
T S KimDepartment of Surgery, University of Washington School of Medicine, 1959 NE Pacific Street, Box 356410, Seattle, WA, 98195, USA.
K J RiehleDepartment of Surgery, University of Washington School of Medicine, 1959 NE Pacific Street, Box 356410, Seattle, WA, 98195, USA.
R S YeungDepartment of Surgery, University of Washington School of Medicine, 1959 NE Pacific Street, Box 356410, Seattle, WA, 98195, USA.
J A CarterDepartment of Surgery, University of Washington School of Medicine, 1959 NE Pacific Street, Box 356410, Seattle, WA, 98195, USA.
K C BarryPublic Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
V G PillarisettyDepartment of Surgery, University of Washington School of Medicine, 1959 NE Pacific Street, Box 356410, Seattle, WA, 98195, USA. vgp@uw.edu.
University of Washington · USFred Hutch Cancer Center · US

Funding

Leica SP8 WWL Confocal MicroscopeS10OD016240 · OD · UNIVERSITY OF WASHINGTON · PI CATTERALL, WILLIAM A · 2014 to 2014
$581k
NIH HHS S10 OD016240
6 · The paper itself

Abstract

Fibrolamellar carcinoma (FLC) is a rare liver tumor driven by the DNAJ-PKAc fusion protein that affects healthy young patients. Little is known about the immune response to FLC, limiting rational design of immunotherapy. Multiplex immunohistochemistry and gene expression profiling were performed to characterize the FLC tumor immune microenvironment and adjacent non-tumor liver (NTL). Flow cytometry and T cell receptor (TCR) sequencing were performed to determine the phenotype of tumor-infiltrating immune cells and the extent of T cell clonal expansion. Fresh human FLC tumor slice cultures (TSCs) were treated with antibodies blocking programmed cell death protein-1 (PD-1) and interleukin-10 (IL-10), with results measured by cleaved caspase-3 immunohistochemistry. Immune cells were concentrated in fibrous stromal bands, rather than in the carcinoma cell compartment. In FLC, T cells demonstrated decreased activation and regulatory T cells in FLC had more frequent expression of PD-1 and CTLA-4 than in NTL. Furthermore, T cells had relatively low levels of clonal expansion despite high TCR conservation across individuals. Combination PD-1 and IL-10 blockade signficantly increased cell death in human FLC TSCs. Immunosuppresion in the FLC tumor microenvironment is characterized by T cell exclusion and exhaustion, which may be reversible with combination immunotherapy.

Indexed as

Carcinoma, HepatocellularInterleukin-10Liver NeoplasmsProgrammed Cell Death 1 ReceptorHumansImmunosuppression TherapyReceptors, Antigen, T-CellTumor MicroenvironmentInterleukin-10Programmed Cell Death 1 ReceptorReceptors, Antigen, T-Cell

Identifiers

PMID38429349
PMCPMC10907637
OpenAlexW4392359526

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.