Evidence map›Paper›PMID 25388653›Full record

ArticleJournal of translational medicine2014

Dual effects of a targeted small-molecule inhibitor (cabozantinib) on immune-mediated killing of tumor cells and immune tumor microenvironment permissiveness when combined with a cancer vaccine.

Anna R Kwilas, Andressa Ardiani, Renee N Donahue, Dana T Aftab, James W Hodge

Registry-linked trialOpen access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of translational medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04197219 (Pembrolizumab With Axitinib in Recurrent Endometrial Cancer With Deficient Mismatch Repair System Post PD1 Exposure), which is not on this map. Cited by 126 papers, 6 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
126citing papers in PubMed, 6 pooled it
2.8field-weighted citation impact, top 9% 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.

NCT04197219 phase2withdrawnnot on this mapstarted 2021, after this paper: background citation

Pembrolizumab With Axitinib in Recurrent Endometrial Cancer With Deficient Mismatch Repair System Post PD1 Exposure: Phase II Trial

TypeinterventionalSponsorCase Comprehensive Cancer CenterRan2021 to 2026Enrolled0ConditionsRecurrent Endometrial CancerArmsPembrolizumab, Axitinib
3 · Its place in the literature

Who cites it

126 citing papers in PubMed, 6 syntheses or guidelines pooled it, 186 citations in OpenAlex.

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  11. Nivolumab Plus Cabozantinib With or Without Ipilimumab for Advanced Hepatocellular Carcinoma: Results From Cohort 6 of the CheckMate 040 Trial.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2023
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  20. Cellular Context Influences Kinase Inhibitor Selectivity.Journal of medicinal chemistry · 2026
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66 more citing papers are in PubMed but not listed here.

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

5 authors at 3 institutions in 2 countries.

Anna R KwilasLaboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 10 Center Drive; Room 8B13, Bethesda, MD, 20892, USA. anna.kwilas@nih.gov.
Andressa ArdianiLaboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 10 Center Drive; Room 8B13, Bethesda, MD, 20892, USA. smith.andressa.a@gmail.com.
Renee N DonahueLaboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 10 Center Drive; Room 8B13, Bethesda, MD, 20892, USA. renee.donahue@nih.gov.
Dana T AftabExelixis, Inc., South San Francisco, CA, USA. daftab@exelixis.com.
James W HodgeLaboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 10 Center Drive; Room 8B13, Bethesda, MD, 20892, USA. jh241d@nih.gov.
Center for Cancer Research · USNational Institutes of Health · USExelixis (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundGrowing awareness of the complexity of carcinogenesis has made multimodal therapies for cancer increasingly compelling and relevant. In recent years, immunotherapy has gained acceptance as an active therapeutic approach to cancer treatment, even though cancer is widely considered an immunosuppressive disease. Combining immunotherapy with targeted agents that have immunomodulatory capabilities could significantly improve its efficacy.

methodsWe evaluated the ability of cabozantinib, a receptor tyrosine kinase inhibitor, to modulate the immune system in vivo as well as alter the phenotype of tumor cells in vitro in order to determine if this inhibitor could act synergistically with a cancer vaccine.

resultsOur studies indicated that cabozantinib altered the phenotype of MC38-CEA murine tumor cells, rendering them more sensitive to immune-mediated killing. Cabozantinib also altered the frequency of immune sub-populations in the periphery as well as in the tumor microenvironment, which generated a more permissive immune environment. When cabozantinib was combined with a poxviral-based cancer vaccine targeting a self-antigen, the combination significantly reduced the function of regulatory T cells and increased cytokine production from effector T cells in response to the antigen. These alterations to the immune landscape, along with direct modification of tumor cells, led to markedly improved antitumor efficacy.

conclusionsThese studies support the clinical combination of cabozantinib with immunotherapy for the treatment of cancer.

Indexed as

Cytotoxicity, ImmunologicTumor MicroenvironmentAnilidesAnimalsBiomarkers, TumorCancer VaccinesCell Line, TumorCell ProliferationCombined Modality TherapyFemaleImmunotherapyLymphocyte SubsetsMice, Inbred C57BLMice, TransgenicNeoplasmsPhenotypeAnilidesBiomarkers, TumorcabozantinibCancer VaccinesPyridinesSmall Molecule Libraries

Identifiers

PMID25388653
PMCPMC4236498
OpenAlexW2102979753

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

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.