Evidence map›Paper›PMID 41701126›Full record

ArticleGastroenterology2026

Overcoming CXCR4-Mediated T-Cell Exclusion Potentiates Antitumor Cytotoxicity in Fibrolamellar Carcinoma.

Jason A Carter, Lindsay K Dickerson, Andreas Stephanou, Sheela R Damle, Kristin E Goodsell, Sara K Daniel, Kevin M Sullivan, Bo Shui, Xiuyun Jiang, Heidi L Kenerson and 19 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Gastroenterology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Review
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

29 authors.

Jason A CarterDepartment of Surgery, University of Washington, Seattle, Washington.
Lindsay K DickersonDepartment of Surgery, University of Washington, Seattle, Washington.
Andreas StephanouDepartment of Biomedical Sciences, Cornell University College of Veterinary Medicine, Ithaca, New York.
Sheela R DamleDepartment of Medicine, University of Washington, Seattle, Washington; Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, Washington.
Kristin E GoodsellDepartment of Surgery, University of Washington, Seattle, Washington.
Sara K DanielDepartment of Surgery, University of Washington, Seattle, Washington.
Kevin M SullivanDepartment of Surgery, University of Washington, Seattle, Washington; Department of Surgery, Louisiana State University Health Sciences Center, New Orleans, Louisiana.
Bo ShuiDepartment of Biomedical Sciences, Cornell University College of Veterinary Medicine, Ithaca, New York.
Xiuyun JiangDepartment of Surgery, University of Washington, Seattle, Washington.
Heidi L KenersonDepartment of Surgery, University of Washington, Seattle, Washington.
Renske J E van den BijgaartPublic Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, Washington.
Alaa R FarghliDepartment of Biomedical Sciences, Cornell University College of Veterinary Medicine, Ithaca, New York.
Yongjun LiuDepartment of Laboratory Medicine and Pathology, University of Washington, Seattle, Washington.
Emily BeirneDepartment of Laboratory Medicine and Pathology, University of Washington, Seattle, Washington.
Kevin P LabadieDepartment of Surgery, University of Washington, Seattle, Washington.
Jack CernakDepartment of Surgery, University of Washington, Seattle, Washington.
Sardar Shahmir B ChauhanDepartment of Surgery, University of Washington, Seattle, Washington.
Jose Mario Bello PinedaMedical Scientist Training Program, University of Washington, Seattle, Washington.
Annalyssa N LongImmunotherapy Integrated Research Center, Fred Hutchinson Cancer Center, Seattle, Washington.
Anna E ElzImmunotherapy Integrated Research Center, Fred Hutchinson Cancer Center, Seattle, Washington.
Evan W NewellPublic Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, Washington; Immunotherapy Integrated Research Center, Fred Hutchinson Cancer Center, Seattle, Washington; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, Washington.
Teresa S KimDepartment of Surgery, University of Washington, Seattle, Washington.
Kimberly J RiehleDepartment of Surgery, University of Washington, Seattle, Washington.
Raymond S YeungDepartment of Surgery, University of Washington, Seattle, Washington.
Shreeram AkileshDepartment of Laboratory Medicine and Pathology, University of Washington, Seattle, Washington.
Ian N CrispeDepartment of Surgery, University of Washington, Seattle, Washington; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, Washington; Department of Immunology, University of Washington, Seattle, Washington.
Kevin C BarryPublic Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, Washington.
Praveen SethupathyDepartment of Biomedical Sciences, Cornell University College of Veterinary Medicine, Ithaca, New York. Electronic address: pr46@cornell.edu.
Venu G PillarisettyDepartment of Surgery, University of Washington, Seattle, Washington. Electronic address: vgp@uw.edu.

Funding

Translational Bioimaging Core Shared ResourceP30CA015704 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI Eric Collisson · 1985 to 2026
$296.4M
Leica SP8 WWL Confocal MicroscopeS10OD016240 · OD · UNIVERSITY OF WASHINGTON · PI CATTERALL, WILLIAM A · 2014 to 2014
$581k
NCI NIH HHS P30 CA015704NIH HHS S10 OD016240
6 · The paper itself

Abstract

BACKGROUND &

aimsFibrolamellar carcinoma (FLC) is a rare liver cancer affecting young adults without underlying cirrhosis. Although almost all FLC patients share an immunogenic DNAJB1-PRKACA fusion oncogene, endogenous antitumor immunity and clinical response to immunotherapy are limited. We hypothesized that the lack of response to immunotherapy is mediated by both T-cell exclusion and intratumoral immunosuppression.

methodsWe used high-throughput single-nucleus RNA sequencing to explore the tumor immune microenvironment (TIME) of FLC. We then used multiplex immunohistochemistry, live imaging, single-cell sequencing, and spatial proteomics in a human tumor slice culture (TSC) system to dissect and experimentally modulate the FLC TIME.

resultsWe identified significant dysregulation of stromal-immune signaling pathways within the FLC TIME relative to adjacent nontumor liver, notably including interactions between CXCL12

conclusionsOur findings demonstrate that immune resistance in FLC is mediated by both local T-cell exclusion and exhaustion, with combination CXCR4 and PD-1 blockade acting cooperatively to overcome these independent mechanisms. These results highlight the versatility of the human TSC system to aid in the study of rare cancer types and provide important preclinical evidence for the rational design of combination immunotherapy in FLC, which currently lacks any effective systemic therapy.

Indexed as

Antineoplastic Combined Chemotherapy ProtocolsCarcinoma, HepatocellularImmune Checkpoint InhibitorsLiver NeoplasmsLymphocytes, Tumor-InfiltratingReceptors, CXCR4T-LymphocytesTumor EscapeChemokine CXCL12Cytotoxicity, ImmunologicHumansMyofibroblastsProgrammed Cell Death 1 ReceptorSignal TransductionTumor MicroenvironmentChemokine CXCL12CXCL12 protein, humanCXCR4 protein, humanImmune Checkpoint InhibitorsPDCD1 protein, humanProgrammed Cell Death 1 ReceptorReceptors, CXCR4Combination ImmunotherapyCXCL12Fibrolamellar CarcinomaTumor Immune Microenvironment

Identifiers

PMID41701126
PMCPMC13546111

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.