Evidence map›Paper›PMID 28129117›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2017

Immunosuppressive Myeloid Cells' Blockade in the Glioma Microenvironment Enhances the Efficacy of Immune-Stimulatory Gene Therapy.

Neha Kamran, Padma Kadiyala, Meghna Saxena, Marianela Candolfi, Youping Li, Mariela A Moreno-Ayala, Nicholas Raja, Diana Shah, Pedro R Lowenstein, Maria G Castro

Open access · bronzeAbstract read
In one paragraph

Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 117 papers.

0numbers the graph read from it
0cells of the map it votes in
117citing papers in PubMed
7.8field-weighted citation impact, top 2% 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

117 citing papers in PubMed, 174 citations in OpenAlex.

  1. Accumulation of amyloid beta in human glioblastomas.Clinical and experimental immunology · 2020
    Trial
  2. Article
  3. Review
  4. Article
  5. Review
  6. Article
  7. Inflammasomes in glioblastoma.Journal of neuroinflammation · 2026
    Review
  8. Article
  9. Article
  10. Frontiers in immunology · 2026
    Article
  11. KITENIN-CCL20 axis is a potential therapeutic target for modulating immunosuppressive tumor microenvironment in glioblastoma.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026
    Article
  12. Review
  13. Review
  14. Article
  15. Review
  16. Review
  17. Breaking Down Glioma-Microenvironment Crosstalk.The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry · 2025
    Review
  18. Article
  19. Article
  20. Article

57 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

10 authors at 2 institutions in 2 countries.

Neha KamranDepartment of Neurosurgery, The University of Michigan School of Medicine, MSRB II, RM 4570C, 1150 West Medical Center Drive, Ann Arbor, MI 48109-5689, USA; Department of Cell and Developmental Biology, The University of Michigan School of Medicine, MSRB II, RM 4570C, 1150 West Medical Center Drive, Ann Arbor, MI 48109-5689, USA.
Padma KadiyalaDepartment of Neurosurgery, The University of Michigan School of Medicine, MSRB II, RM 4570C, 1150 West Medical Center Drive, Ann Arbor, MI 48109-5689, USA; Department of Cell and Developmental Biology, The University of Michigan School of Medicine, MSRB II, RM 4570C, 1150 West Medical Center Drive, Ann Arbor, MI 48109-5689, USA.
Meghna SaxenaDepartment of Neurosurgery, The University of Michigan School of Medicine, MSRB II, RM 4570C, 1150 West Medical Center Drive, Ann Arbor, MI 48109-5689, USA; Department of Cell and Developmental Biology, The University of Michigan School of Medicine, MSRB II, RM 4570C, 1150 West Medical Center Drive, Ann Arbor, MI 48109-5689, USA.
Marianela CandolfiInstituto de Investigaciones Biomédicas (CONICET-UBA), Facultad de Medicina, Universidad de Buenos Aires, 1053 Buenos Aires, Argentina.
Youping LiDepartment of Neurosurgery, The University of Michigan School of Medicine, MSRB II, RM 4570C, 1150 West Medical Center Drive, Ann Arbor, MI 48109-5689, USA; Department of Cell and Developmental Biology, The University of Michigan School of Medicine, MSRB II, RM 4570C, 1150 West Medical Center Drive, Ann Arbor, MI 48109-5689, USA.
Mariela A Moreno-AyalaDepartment of Neurosurgery, The University of Michigan School of Medicine, MSRB II, RM 4570C, 1150 West Medical Center Drive, Ann Arbor, MI 48109-5689, USA; Department of Cell and Developmental Biology, The University of Michigan School of Medicine, MSRB II, RM 4570C, 1150 West Medical Center Drive, Ann Arbor, MI 48109-5689, USA; Instituto de Investigaciones Biomédicas (CONICET-UBA), Facultad de Medicina, Universidad de Buenos Aires, 1053 Buenos Aires, Argentina.
Nicholas RajaDepartment of Neurosurgery, The University of Michigan School of Medicine, MSRB II, RM 4570C, 1150 West Medical Center Drive, Ann Arbor, MI 48109-5689, USA; Department of Cell and Developmental Biology, The University of Michigan School of Medicine, MSRB II, RM 4570C, 1150 West Medical Center Drive, Ann Arbor, MI 48109-5689, USA.
Diana ShahDepartment of Neurosurgery, The University of Michigan School of Medicine, MSRB II, RM 4570C, 1150 West Medical Center Drive, Ann Arbor, MI 48109-5689, USA; Department of Cell and Developmental Biology, The University of Michigan School of Medicine, MSRB II, RM 4570C, 1150 West Medical Center Drive, Ann Arbor, MI 48109-5689, USA.
Pedro R LowensteinDepartment of Neurosurgery, The University of Michigan School of Medicine, MSRB II, RM 4570C, 1150 West Medical Center Drive, Ann Arbor, MI 48109-5689, USA; Department of Cell and Developmental Biology, The University of Michigan School of Medicine, MSRB II, RM 4570C, 1150 West Medical Center Drive, Ann Arbor, MI 48109-5689, USA.
Maria G CastroDepartment of Neurosurgery, The University of Michigan School of Medicine, MSRB II, RM 4570C, 1150 West Medical Center Drive, Ann Arbor, MI 48109-5689, USA; Department of Cell and Developmental Biology, The University of Michigan School of Medicine, MSRB II, RM 4570C, 1150 West Medical Center Drive, Ann Arbor, MI 48109-5689, USA. Electronic address: mariacas@umich.edu.
University of Michigan–Ann Arbor · USInstitute of Astronomy and Space Physics · AR

Funding

XenograftP30CA046592 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI THEODORE S LAWRENCE · 1988 to 2026
$178.2M
Michigan Institute for Clinical and Health Research (MCHR)UL1TR000433 · NCATS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI MASHOUR, GEORGE ALEXANDER · 2012 to 2016
$49.9M
MICHIGAN MEDICAL SCIENTIST TRAINING PROGRAMT32GM007863 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI COLLINS, KATHLEEN L. · 1985 to 2024
$38.3M
TRAINING IN CLINICAL AND BASIC NEUROSCIENCET32NS007222 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Henry L Paulson · 1985 to 2026
$8.0M
Training Program in Tumor MicroenvironmentT32CA009676 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Maria G Castro, Analisa Virginia DiFeo · 1992 to 2026
$7.3M
Oligodendrocyte-focused rAAV gene therapy strategies for Canavan disease and LeukodystrophiesR01NS076991 · NINDS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI Guangping Gao · 2012 to 2026
$5.7M
Immune-suppressive Myeloid Cells in the Glioma Microenvironment: Signaling Mechanisms and Novel Therapeutic StrategiesR37NS094804 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI CASTRO, MARIA G · 2015 to 2021
$2.9M
Neuroimmunology of Malignant Brain Tumors: Innate MechanismsR01NS096756 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI LOWENSTEIN, PEDRO R. · 2016 to 2020
$2.1M
Engineering the Brain Immune System for Tumor TherapyR01NS057711 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI CASTRO, MARIA G · 2009 to 2013
$2.0M
Crosstalk between glioma cells & immune cells in the tumor microenvironment: TherR01NS074387 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI CASTRO, MARIA G · 2011 to 2015
$1.9M
Brain immune responses:Cellular & Molecular MechanismsR01NS061107 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI LOWENSTEIN, PEDRO R. · 2008 to 2012
$1.7M
Mechanisms of glioma growth and invasion novel therapeutic strategiesR01NS082311 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI LOWENSTEIN, PEDRO R. · 2013 to 2017
$1.7M
NCATS NIH HHS UL1 TR000433NCI NIH HHS P30 CA046592NCI NIH HHS T32 CA009676NIBIB NIH HHS R01 EB022563NIGMS NIH HHS T32 GM007863NINDS NIH HHS R01 NS057711NINDS NIH HHS R01 NS061107NINDS NIH HHS R01 NS074387NINDS NIH HHS R01 NS076991NINDS NIH HHS R01 NS082311NINDS NIH HHS R01 NS096756NINDS NIH HHS R21 NS084275NINDS NIH HHS R21 NS091555NINDS NIH HHS R37 NS094804NINDS NIH HHS T32 NS007222
6 · The paper itself

Abstract

Survival of glioma (GBM) patients treated with the current standard of care remains dismal. Immunotherapeutic approaches that harness the cytotoxic and memory potential of the host immune system have shown great benefit in other cancers. GBMs have developed multiple strategies, including the accumulation of myeloid-derived suppressor cells (MDSCs) to induce immunosuppression. It is therefore imperative to develop multipronged approaches when aiming to generate a robust anti-tumor immune response. Herein, we tested whether combining MDSC depletion or checkpoint blockade would augment the efficacy of immune-stimulatory herpes simplex type-I thymidine kinase (TK) plus Fms-like tyrosine kinase ligand (Flt3L)-mediated immune stimulatory gene therapy. Our results show that MDSCs constitute >40% of the tumor-infiltrating immune cells. These cells express IL-4Rα, inducible nitric oxide synthase (iNOS), arginase, programmed death ligand 1 (PDL1), and CD80, molecules that are critically involved in antigen-specific T cell suppression. Depletion of MDSCs strongly enhanced the TK/Flt3L gene therapy-induced tumor-specific CD8 T cell response, which lead to increased median survival and percentage of long-term survivors. Also, combining PDL1 or CTLA-4 immune checkpoint blockade greatly improved the efficacy of TK/Flt3L gene therapy. Our results, therefore, indicate that blocking MDSC-mediated immunosuppression holds great promise for increasing the efficacy of gene therapy-mediated immunotherapies for GBM.

Indexed as

Genetic TherapyAnimalsB7-H1 AntigenBiomarkersBone Marrow CellsBrain NeoplasmsCells, CulturedCTLA-4 AntigenCytotoxicity, ImmunologicFemaleGene ExpressionGliomaHumansImmunophenotypingImmunosuppression TherapyImmunotherapyB7-H1 AntigenBiomarkersCTLA-4 Antigenflt3 ligand proteinMembrane ProteinsThymidine Kinasegene therapygliomaimmunotherapymyeloid cellstumor microenvironment

Identifiers

PMID28129117
PMCPMC5363306
OpenAlexW2569426717

What OpenQuestion holds

Textmetadata
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.