Evidence map›Paper›PMID 27522581›Full record

Trial reportCancer immunology, immunotherapy : CII2016

Intratumoral interferon-gamma increases chemokine production but fails to increase T cell infiltration of human melanoma metastases.

Ileana S Mauldin, Nolan A Wages, Anne M Stowman, Ena Wang, Mark E Smolkin, Walter C Olson, Donna H Deacon, Kelly T Smith, Nadedja V Galeassi, Kimberly A Chianese-Bullock and 5 more

Open access · greenAbstract readClinical Trial
In one paragraph

Trial report in Cancer immunology, immunotherapy : CII, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed
2.0field-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

35 citing papers in PubMed, 49 citations in OpenAlex.

  1. Trial
  2. Adaptive resistance in cancer immunotherapy.Cellular & molecular immunology · 2026
    Review
  3. Monitoring T-Cell Activation in the Tumor Microenvironment by PET Imaging of the Chemokine CXCL9.Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2025
    Article
  4. Review
  5. Article
  6. Article
  7. Review
  8. Barriers to immune cell infiltration in tumors.Journal for immunotherapy of cancer · 2023
    Review
  9. Article
  10. Article
  11. Article
  12. Review
  13. Review
  14. Article
  15. Review
  16. Review
  17. Review
  18. Article
  19. Differentiation and Regulation of TFrontiers in immunology · 2021
    Review
  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

15 authors at 3 institutions in 2 countries.

Ileana S MauldinDepartment of Surgery/Division of Surgical Oncology and the Human Immune Therapy Center, Cancer Center, University of Virginia, 1352 Jordan Hall, P.O. Box 801457, Charlottesville, VA, 22908, USA.
Nolan A WagesDepartment of Public Health Sciences, University of Virginia, Charlottesville, VA, USA.
Anne M StowmanDepartment of Surgery/Division of Surgical Oncology and the Human Immune Therapy Center, Cancer Center, University of Virginia, 1352 Jordan Hall, P.O. Box 801457, Charlottesville, VA, 22908, USA.
Ena WangResearch Branch, Sidra Medical and Research Center, Doha, Qatar.
Mark E SmolkinDepartment of Public Health Sciences, University of Virginia, Charlottesville, VA, USA.
Walter C OlsonDepartment of Surgery/Division of Surgical Oncology and the Human Immune Therapy Center, Cancer Center, University of Virginia, 1352 Jordan Hall, P.O. Box 801457, Charlottesville, VA, 22908, USA.
Donna H DeaconDepartment of Surgery/Division of Surgical Oncology and the Human Immune Therapy Center, Cancer Center, University of Virginia, 1352 Jordan Hall, P.O. Box 801457, Charlottesville, VA, 22908, USA.
Kelly T SmithDepartment of Surgery/Division of Surgical Oncology and the Human Immune Therapy Center, Cancer Center, University of Virginia, 1352 Jordan Hall, P.O. Box 801457, Charlottesville, VA, 22908, USA.
Nadedja V GaleassiDepartment of Surgery/Division of Surgical Oncology and the Human Immune Therapy Center, Cancer Center, University of Virginia, 1352 Jordan Hall, P.O. Box 801457, Charlottesville, VA, 22908, USA.
Kimberly A Chianese-BullockDepartment of Surgery/Division of Surgical Oncology and the Human Immune Therapy Center, Cancer Center, University of Virginia, 1352 Jordan Hall, P.O. Box 801457, Charlottesville, VA, 22908, USA.
Lynn T DengelDepartment of Surgery/Division of Surgical Oncology and the Human Immune Therapy Center, Cancer Center, University of Virginia, 1352 Jordan Hall, P.O. Box 801457, Charlottesville, VA, 22908, USA.
Francesco M MarincolaResearch Branch, Sidra Medical and Research Center, Doha, Qatar.
Gina R PetroniDepartment of Public Health Sciences, University of Virginia, Charlottesville, VA, USA.
David W MullinsDepartment of Microbiology and Immunology, Norris Cotton Cancer Center, Geisel School of Medicine at Dartmouth, Lebanon, NH, USA.
Craig L SlingluffDepartment of Surgery/Division of Surgical Oncology and the Human Immune Therapy Center, Cancer Center, University of Virginia, 1352 Jordan Hall, P.O. Box 801457, Charlottesville, VA, 22908, USA. cls8h@virginia.edu.ORCID 0000-0002-6664-4373
University of Virginia · USSidra Medical and Research Center · QADartmouth College · US

Funding

Women's Oncology Program - WONP30CA044579 · NCI · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI Jay William FOX · 1987 to 2026
$72.1M
Cancer Research Training Program: From Molecular Mechanisms to Therapeutic StrategiesT32CA009109 · NCI · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI Andrew Carl Dudley, Melanie R Rutkowski · 1985 to 2026
$13.9M
Role of CXCR3 for CD8+ T cells in cancer immunotherapyR01CA134799 · NCI · UNIVERSITY OF VIRGINIA · PI MULLINS, DAVID W. · 2009 to 2013
$1.6M
Phase I Designs for Combined Immunotherapies in CancerK25CA181638 · NCI · UNIVERSITY OF VIRGINIA · PI WAGES, NOLAN · 2014 to 2018
$780k
NCI NIH HHS K25 CA181638NCI NIH HHS P30 CA044579NCI NIH HHS R01 CA134799NCI NIH HHS T32 CA009109
6 · The paper itself

Abstract

introductionOptimal approaches to induce T cell infiltration of tumors are not known. Chemokines CXCL9, CXCL10, and CXCL11 support effector T cell recruitment and may be induced by IFN. This study tests the hypothesis that intratumoral administration of IFNγ will induce CXCL9-11 and will induce T cell recruitment and anti-tumor immune signatures in melanoma metastases. PATIENTS AND

methodsNine eligible patients were immunized with a vaccine comprised of 12 class I MHC-restricted melanoma peptides and received IFNγ intratumorally. Effects on the tumor microenvironment were evaluated in sequential tumor biopsies. Adverse events (AEs) were recorded. T cell responses to vaccination were assessed in PBMC by IFNγ ELISPOT assay. Tumor biopsies were evaluated for immune cell infiltration, chemokine protein expression, and gene expression.

resultsVaccination and intratumoral administration of IFNγ were well tolerated. Circulating T cell responses to vaccine were detected in six of nine patients. IFNγ increased production of chemokines CXCL10, CXCL11, and CCL5 in patient tumors. Neither vaccination alone, nor the addition of IFNγ promoted immune cell infiltration or induced anti-tumor immune gene signatures.

conclusionThe melanoma vaccine induced circulating T cell responses, but it failed to infiltrate metastases, thus highlighting the need for combination strategies to support T cell infiltration. A single intratumoral injection of IFNγ induced T cell-attracting chemokines; however, it also induced secondary immune regulation that may paradoxically limit immune infiltration and effector functions. Alternate dosing strategies or additional combinatorial treatments may be needed to promote trafficking and retention of tumor-reactive T cells in melanoma metastases.

Indexed as

AgedAged, 80 and overAntigens, NeoplasmCancer VaccinesCell MovementCells, CulturedChemokine CCL5Chemokine CXCL10Chemokine CXCL11Enzyme-Linked Immunospot AssayFemaleFollow-Up StudiesHumansImmunologic FactorsImmunotherapyInterferon-gammaAntigens, NeoplasmCancer VaccinesCCL5 protein, humanChemokine CCL5Chemokine CXCL10Chemokine CXCL11CXCL10 protein, humanCXCL11 protein, humanImmunologic FactorsInterferon-gammaPeptide FragmentsVaccines, SubunitHumanImmunotherapyInterferon-gammaMelanomaT lymphocytesTumor vaccines

Identifiers

PMID27522581
PMCPMC5037033
OpenAlexW2510964254

What OpenQuestion holds

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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.