Evidence map›Paper›PMID 41142777›Full record

ArticleFrontiers in immunology2025

Multimodal reprogramming of the tumor microenvironment by MMR and dual checkpoint blockade in hepatocellular carcinoma models.

Mulu Z Tesfay, Aleksandra Cios, Khandoker Usran Ferdous, Randal S Shelton, Bahaa Mustafa, Camila C Simoes, Murat Gokden, Isabelle R Miousse, Kimberly J Krager, Marjan Boerma and 18 more

Abstract read
In one paragraph

Article in Frontiers in immunology, 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. 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

28 authors.

Mulu Z TesfayDepartment of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR, United States.
Aleksandra CiosDepartment of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR, United States.
Khandoker Usran FerdousDepartment of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR, United States.
Randal S SheltonDepartment of Pharmaceutical Sciences, Division of Radiation Health, University of Arkansas for Medical Sciences, Little Rock, AR, United States.
Bahaa MustafaWintrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, Little Rock, AR, United States.
Camila C SimoesDepartment of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR, United States.
Murat GokdenDepartment of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR, United States.
Isabelle R MiousseWintrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, Little Rock, AR, United States.
Kimberly J KragerDepartment of Pharmaceutical Sciences, Division of Radiation Health, University of Arkansas for Medical Sciences, Little Rock, AR, United States.
Marjan BoermaWintrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, Little Rock, AR, United States.
Alicja UrbaniakWintrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, Little Rock, AR, United States.
Anuradha KunthurDepartment of Hematology and Oncology, University of Arkansas for Medical Sciences, Little Rock, AR, United States.
Sri ObulareddyDepartment of Hematology and Oncology, University of Arkansas for Medical Sciences, Little Rock, AR, United States.
Joshua M EichhornCollege of Medicine, Radiology, University of Arkansas for Medical Sciences, Little Rock, AR, United States.
Steven R PostDepartment of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR, United States.
Jean Christopher ChamcheuDepartment of Pathological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, United States.
Omeed MoavenDivision of Surgical Oncology, Department of Surgery, Louisiana State University, Health Science Center, New Orleans, LA, United States.
Chiswili Y ChabuDivision of Biological Sciences, University of Missouri, Columbia, MO, United States.
Dan G DudaSteele Laboratories for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States.
Matteo ContiPublic Health Department, Azienda Unita' Sanitaria Locale Imola, Imola, Italy.
Bruno NardoDepartment of Pharmacy, Health and Nutritional Sciences, University of Calabria, Rende, Italy.
Rang GovindarajanWintrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, Little Rock, AR, United States.
Martin E Fernandez-ZapicoSchulze Center for Novel Therapeutics, Division of Oncology Research, Mayo Clinic, Rochester, MN, United States.
Lewis R RobertsDepartment of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, United States.
Mitesh J BoradDepartment of Hematology and Medical Oncology, Mayo Clinic, Phoenix, AZ, United States.
Martin J CannonWintrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, Little Rock, AR, United States.
Alexei G BasnakianWintrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, Little Rock, AR, United States.
Bolni M NagaloDepartment of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR, United States.

Funding

Unraveling Gene-Environment Interactions Shaping Metabolism: A Multi-Omics Analysis in DrosophilaP20GM139768 · NIGMS · UNIVERSITY OF ARKANSAS AT FAYETTEVILLE · PI Joanna Fiddler · 2021 to 2026
$17.0M
BLRD VA I01 BX002425BLRD VA IK6 BX006184NIGMS NIH HHS P20 GM139768
6 · The paper itself

Abstract

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide, thus, there is an urgent need to develop more effective therapeutic options for this dismal condition. Tumor-infiltrating lymphocytes (TILs) are associated with improved response to immune checkpoint blockade in HCC, but their low abundance in most cases limits their therapeutic efficacy. Here, we demonstrate, in mice, that low-dose intratumoral immunovirotherapy with the trivalent measles, mumps, and rubella vaccine (MMR) induces superior tumor-growth delay and extended host survival compared to individually administered vaccines for measles, mumps, or rubella viruses. Further, our results show that MMR therapy synergizes with PD-1 and CTLA-4 blockade to reprogram the tumor microenvironment, resulting in increased CD8+ TIL infiltration and reduced PD-1 expression on TILs, among other effects. These changes in the immunological landscape translated into greater survival and more durable tumor-specific and memory immune responses for hosts. Comprehensive toxicology analysis revealed no evidence of MMR-induced liver or kidney toxicity after intrahepatic administration. This work reinforces an unrecognized role of MMR plus ICB in reprogramming the immune landscape in HCC through multimodal immune activation, providing a strong rationale for further development of MMR-based therapies for HCC.

Indexed as

Carcinoma, HepatocellularImmune Checkpoint InhibitorsLiver NeoplasmsTumor MicroenvironmentAnimalsCD8-Positive T-LymphocytesCell Line, TumorCTLA-4 AntigenDisease Models, AnimalHumansImmunotherapyLymphocytes, Tumor-InfiltratingMiceMice, Inbred C57BLProgrammed Cell Death 1 ReceptorCTLA-4 AntigenImmune Checkpoint InhibitorsProgrammed Cell Death 1 Receptorhepatocellular carcinomaimmune checkpoint blockadeinnate and adaptive immunity modulationMMR vaccinetumor microenvironment

Identifiers

PMID41142777
PMCPMC12546120

What Socratic 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 Socratic graph.