Evidence map›Paper›PMID 37790490›Full record

ArticleResearch square2023

Dendritic Cell Vaccination in Conjunction with a TLR Agonist Polarizes Interferon Immune Responses in Malignant Glioma Patients.

Richard G Everson, Willy Hugo, Lu Sun, Joseph Antonios, Alexander Lee, Lizhong Ding, Melissa Bu, Sarah Khattab, Carolina Chavez, Emma Billingslea-Yoon and 5 more

Registry-linked trialOpen access · greenAbstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in Research square, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01204684 (A Phase II Clinical Trial Evaluating Autologous Dendritic Cells Pulsed With Tumor Lysate Antigen +/- Toll-like Receptor Agonists for the Treatment of Malignant Glioma), which is not on this map. Not yet cited in PubMed.

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

NCT01204684 phase2completednot on this map

A Phase II Clinical Trial Evaluating Autologous Dendritic Cells Pulsed With Tumor Lysate Antigen +/- Toll-like Receptor Agonists for the Treatment of Malignant Glioma

TypeinterventionalSponsorJonsson Comprehensive Cancer CenterRan2010 to 2024Enrolled24ConditionsGlioma, Anaplastic Astrocytoma, Anaplastic Astro-oligodendroglioma, GlioblastomaArmsautologous tumor lysate-pulsed DC vaccination, Tumor lysate-pulsed DC vaccination+0.2% resiquimod, Tumor-lysate pulsed DC vaccination +adjuvant polyICLC
3 · Its place in the literature

Who cites it

0 citing papers in PubMed, 1 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors at 3 institutions in 1 country.

Richard G EversonDepartment of Neurosurgery, David Geffen School of Medicine at UCLA, University of California Los Angeles, Los Angeles, California, 90095, U.S.A.ORCID 0000-0003-2809-3061
Willy HugoJonsson Comprehensive Cancer Center, David Geffen School of Medicine at UCLA, University of California Los Angeles, Los Angeles, California, 90095, U.S.A.ORCID 0000-0002-1426-7190
Lu SunDepartment of Neurosurgery, David Geffen School of Medicine at UCLA, University of California Los Angeles, Los Angeles, California, 90095, U.S.A.
Joseph AntoniosDepartment of Neurosurgery, David Geffen School of Medicine at UCLA, University of California Los Angeles, Los Angeles, California, 90095, U.S.A.
Alexander LeeDepartment of Neurosurgery, David Geffen School of Medicine at UCLA, University of California Los Angeles, Los Angeles, California, 90095, U.S.A.ORCID 0000-0002-4583-0740
Lizhong DingDepartment of Medicine, Division of Dermatology, David Geffen School of Medicine at UCLA, University of California Los Angeles, Los Angeles, California, 90095, U.S.A.
Melissa BuDepartment of Medicine, Division of Dermatology, David Geffen School of Medicine at UCLA, University of California Los Angeles, Los Angeles, California, 90095, U.S.A.
Sarah KhattabDepartment of Neurosurgery, David Geffen School of Medicine at UCLA, University of California Los Angeles, Los Angeles, California, 90095, U.S.A.
Carolina ChavezDepartment of Molecular and Medical Pharmacology , David Geffen School of Medicine at UCLA, University of California Los Angeles, Los Angeles, California, 90095, U.S.A.
Emma Billingslea-YoonDepartment of Neurosurgery, David Geffen School of Medicine at UCLA, University of California Los Angeles, Los Angeles, California, 90095, U.S.A.
Andres SalazarOncovir, Inc., Winchester, VA.
Benjamin M EllingsonJonsson Comprehensive Cancer Center, David Geffen School of Medicine at UCLA, University of California Los Angeles, Los Angeles, California, 90095, U.S.A.
Timothy F CloughesyDepartment of Molecular and Medical Pharmacology , David Geffen School of Medicine at UCLA, University of California Los Angeles, Los Angeles, California, 90095, U.S.A.ORCID 0000-0002-8656-7483
Linda M LiauDepartment of Neurosurgery, David Geffen School of Medicine at UCLA, University of California Los Angeles, Los Angeles, California, 90095, U.S.A.ORCID 0000-0002-4053-0052
Robert M PrinsDepartment of Neurosurgery, David Geffen School of Medicine at UCLA, University of California Los Angeles, Los Angeles, California, 90095, U.S.A.ORCID 0000-0002-6282-6583
University of California, Los Angeles · USUCLA Health · USOncovir (United States) · US

Funding

Women's CancersP30CA016042 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Samuel Wheeler French · 1985 to 2026
$134.5M
UCLA Clinical Translational Science InstituteUL1TR001881 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ARLEEN F. BROWN, ARASH NAEIM · 2016 to 2026
$118.1M
UCLA SPORE in Brain CancerP50CA211015 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Yvonne Yu-Hsuan Chen · 2017 to 2026
$25.2M
UCLA Tumor Immunology Training ProgramT32CA009120 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Steven M. Dubinett, MICHAEL A TEITELL · 1985 to 2026
$10.3M
Quantitative molecular MR-PET imaging of glycolysis in glioblastomaR01CA279984 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Benjamin M. Ellingson, David A. Nathanson · 2023 to 2026
$2.4M
Metastatic Clonal Heterogeneity and its Impact on Melanoma Therapeutic ResistanceR01CA236910 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI HUGO, WILLY · 2020 to 2024
$2.3M
CNS Anti-tumor immunity induced by dendritic cell vaccination and TLR agonistsR01CA123396 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI PRINS, ROBERT M · 2007 to 2010
$939k
NCATS NIH HHS UL1 TR001881NCI NIH HHS P30 CA016042NCI NIH HHS P50 CA211015NCI NIH HHS R01 CA123396NCI NIH HHS R01 CA236910NCI NIH HHS R01 CA279984NCI NIH HHS T32 CA009120
6 · The paper itself

Abstract

Autologous tumor lysate-pulsed dendritic cell (ATL-DC) vaccination is a promising immunotherapy for patients with high grade gliomas, but responses have not been demonstrated in all patients. To determine the most effective combination of autologous tumor lysate-pulsed DC vaccination, with or without the adjuvant toll-like receptor (TLR) agonists poly-ICLC or resiquimod, we conducted a Phase 2 clinical trial in 23 patients with newly diagnosed or recurrent WHO Grade III-IV malignant gliomas. We then performed deep, high-dimensional immune profiling of these patients to better understand how TLR agonists may influence the systemic immune responses induced by ATL-DC vaccination. Bulk RNAseq data demonstrated highly significant upregulation of type 1 and type 2 interferon gene expression selectively in patients who received adjuvant a TLR agonist together with ATL-DC. CyTOF analysis of patient peripheral blood mononuclear cells (PBMCs) showed increased expression of PD-1 on CD4+ T-cells, decreases in CD38 and CD39 on CD8+ T cells and elevated proportion of monocytes after ATL-DC + TLR agonist administration. In addition, scRNA-seq demonstrated a higher expression fold change of IFN-induced genes with poly-ICLC treatment in both peripheral blood monocytes and T lymphocytes. Patients who had higher expression of interferon response genes lived significantly longer and had longer time to progression compared to those with lower expression. The results suggest that ATL-DC in conjunction with adjuvant poly-ICLC induces a polarized interferon response in circulating monocytes and specific activation of a CD8+ T cell population, which may represent an important blood biomarker for immunotherapy in this patient population.

trial registrationClinicalTrials.gov Identifier: NCT01204684.

Indexed as

brain cancergliomaimmunotherapyTLR agonist

Identifiers

PMID37790490
PMCPMC10543402
OpenAlexW4386690738

What OpenQuestion holds

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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.