Evidence map›Paper›PMID 25092771›Full record

ArticleCancer immunology research2014

Immune consequences of decreasing tumor vasculature with antiangiogenic tyrosine kinase inhibitors in combination with therapeutic vaccines.

Benedetto Farsaci, Renee N Donahue, Michael A Coplin, Italia Grenga, Lauren M Lepone, Alfredo A Molinolo, James W Hodge

Open access · bronzeAbstract read
In one paragraph

Article in Cancer immunology research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.

0numbers the graph read from it
0cells of the map it votes in
60citing papers in PubMed
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.

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

60 citing papers in PubMed, 80 citations in OpenAlex.

  1. Trial
  2. Trial
  3. Review
  4. Article
  5. Article
  6. Article
  7. Review
  8. Small-molecule-based targeted therapy in liver cancer.Molecular therapy : the journal of the American Society of Gene Therapy · 2024
    Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Review
  17. Review
  18. Immune-awakeninActa pharmaceutica Sinica. B · 2022
    Article
  19. Article
  20. 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

7 authors at 1 institution in 1 country.

Benedetto FarsaciLaboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland.
Renee N DonahueLaboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland.
Michael A CoplinLaboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland.
Italia GrengaLaboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland.
Lauren M LeponeLaboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland.
Alfredo A MolinoloOral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, NIH, Bethesda, Maryland.
James W HodgeLaboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland. jh241d@nih.gov.
National Institute of Dental and Craniofacial Research · US

Funding

Vaccine and Drug Combination Therapy for Human CancersZIABC010661 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI HODGE, JAMES · 2009 to 2025
$11.2M
Vaccine and Drug Combination Therapy for Human CancersZ01BC010661 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI HODGE, JAMES W · 2005 to 2008
$1.8M
Intramural NIH HHS Z01 BC010661Intramural NIH HHS Z99 CA999999Intramural NIH HHS ZIA BC010661NCI NIH HHS Z01 BC010661-04
6 · The paper itself

Abstract

This study investigated the effects on the tumor microenvironment (TME) of combining antiangiogenic tyrosine kinase inhibitors (TKI) with therapeutic vaccines, and in particular, how vascular changes affect tumor-infiltrating immune cells. We conducted studies using a TKI (sunitinib or sorafenib) in combination with recombinant vaccines in two murine tumor models: colon carcinoma (MC38-CEA) and breast cancer (4T1). Tumor vasculature was measured by immunohistochemistry using three endothelial cell markers: CD31 (mature), CD105 (immature/proliferating), and CD11b (monocytic). We assessed oxygenation, tight junctions, compactness, and pressure within tumors, along with the frequency and phenotype of tumor-infiltrating lymphocytes (TIL), myeloid-derived suppressor cells (MDSC), and tumor-associated macrophages (TAM) following treatment with antiangiogenic TKIs alone, vaccine alone, or the combination of a TKI with vaccine. The combined regimen decreased tumor vasculature, compactness, tight junctions, and pressure, leading to vascular normalization and increased tumor oxygenation. This combination therapy also increased TILs, including tumor antigen-specific CD8 T cells, and elevated the expression of activation markers FAS-L, CXCL-9, CD31, and CD105 in MDSCs and TAMs, leading to reduced tumor volumes and an increase in the number of tumor-free animals. The improved antitumor activity induced by combining antiangiogenic TKIs with vaccine may be the result of activated lymphoid and myeloid cells in the TME, resulting from vascular normalization, decreased tumor-cell density, and the consequent improvement in vascular perfusion and oxygenation. Therapies that alter tumor architecture can, thus, have a dramatic impact on the effectiveness of cancer immunotherapy.

Indexed as

Angiogenesis InhibitorsAnimalsCancer VaccinesCell Line, TumorCombined Modality TherapyFemaleFlow CytometryHumansIndolesLymphocytes, Tumor-InfiltratingMiceMice, Inbred C57BLMice, TransgenicNeoplasms, ExperimentalNiacinamidePhenylurea CompoundsAngiogenesis InhibitorsCancer VaccinesIndolesNiacinamidePhenylurea CompoundsProtein Kinase InhibitorsProtein-Tyrosine KinasesPyrrolesSorafenibSunitinibVaccines, Synthetic

Identifiers

PMID25092771
PMCPMC4221465
OpenAlexW2324902637

What OpenQuestion holds

Textmetadata
LicenceTDM
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.