Evidence map›Paper›PMID 36791206›Full record

ArticleScience translational medicine2023

Small-molecule toosendanin reverses macrophage-mediated immunosuppression to overcome glioblastoma resistance to immunotherapy.

Fan Yang, Duo Zhang, Haowen Jiang, Jiangbin Ye, Lin Zhang, Stephen J Bagley, Jeffery Winkler, Yanqing Gong, Yi Fan

Open access · greenAbstract read
In one paragraph

Article in Science translational medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
41citing papers in PubMed, 1 pooled it
9.4field-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

41 citing papers in PubMed, 1 synthesis or guideline pooled it, 57 citations in OpenAlex.

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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

9 authors at 2 institutions in 1 country.

Fan YangDepartment of Radiation Oncology, University of Pennsylvania, Philadelphia, PA 19104, USA.ORCID 0000-0003-3106-7593
Duo ZhangDepartment of Radiation Oncology, University of Pennsylvania, Philadelphia, PA 19104, USA.ORCID 0000-0003-3215-2466
Haowen JiangDepartment of Radiation Oncology, Stanford University, Stanford, CA 94305, USA.ORCID 0000-0003-4021-3820
Jiangbin YeDepartment of Radiation Oncology, Stanford University, Stanford, CA 94305, USA.ORCID 0000-0003-1117-4869
Lin ZhangDepartment of Obstetrics and Gynecology, University of Pennsylvania, Philadelphia, PA 19104, USA.
Stephen J BagleyAbramson Cancer Center, University of Pennsylvania, Philadelphia, PA 19104, USA.ORCID 0000-0002-7117-0539
Jeffery WinklerDepartment of Chemistry, University of Pennsylvania, Philadelphia, PA 19104, USA.ORCID 0000-0001-8264-5491
Yanqing GongDepartment of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Yi FanDepartment of Radiation Oncology, University of Pennsylvania, Philadelphia, PA 19104, USA.ORCID 0000-0002-6290-0595
University of Pennsylvania · USStanford University · US

Funding

Phenotypic Diversity in COVID-19UL1TR001878 · NCATS · UNIVERSITY OF PENNSYLVANIA · PI FITZGERALD, GARRET A · 2016 to 2025
$102.4M
Endothelial plasticity in glioma vascularization and therapy resistanceR01NS094533 · NINDS · UNIVERSITY OF PENNSYLVANIA · PI Yi Fan · 2015 to 2026
$4.3M
Endothelial plasticity in cardiac repair after myocardial infarctionR01HL155198 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI FAN, YI, GONG, YANQING · 2021 to 2024
$2.4M
Dissecting the biology and consequence of circulating glioma cellsR01CA241501 · NCI · UNIVERSITY OF PENNSYLVANIA · PI DORSEY, JAY FITZGERALD, FAN, YI · 2020 to 2024
$2.3M
Macrophage polarization in glioma microenvironmentR01NS106108 · NINDS · UNIVERSITY OF PENNSYLVANIA · PI FAN, YI · 2018 to 2022
$2.0M
NCATS NIH HHS UL1 TR001878NCI NIH HHS R01 CA241501NHLBI NIH HHS R01 HL155198NINDS NIH HHS R01 NS094533NINDS NIH HHS R01 NS106108
6 · The paper itself

Abstract

T cell-based immunotherapy holds promise for treating solid tumors, but its therapeutic efficacy is limited by intratumoral immune suppression. This immune suppressive tumor microenvironment is largely driven by tumor-associated myeloid cells, including macrophages. Here, we report that toosendanin (TSN), a small-molecule compound, reprograms macrophages to enforce antitumor immunity in glioblastoma (GBM) in mouse models. Our functional screen of genetically probed macrophages with a chemical library identifies that TSN reverses macrophage-mediated tumor immunosuppression, leading to enhanced T cell infiltration, activation, and reduced exhaustion. Chemoproteomic and structural analyses revealed that TSN interacts with Hck and Lyn to abrogate suppressive macrophage immunity. In addition, a combination of immune checkpoint blockade and TSN therapy induced regression of syngeneic GBM tumors in mice. Furthermore, TSN treatment sensitized GBM to Egfrviii chimeric antigen receptor (CAR) T cell therapy. These findings suggest that TSN may serve as a therapeutic compound that blocks tumor immunosuppression and circumvents tumor resistance to T cell-based immunotherapy in GBM and other solid tumors that warrants further investigation.

Indexed as

Brain NeoplasmsGlioblastomaAnimalsCell Line, TumorImmunosuppression TherapyImmunotherapyImmunotherapy, AdoptiveMacrophagesMiceTriterpenesTumor MicroenvironmenttoosendaninTriterpenes

Identifiers

PMID36791206
PMCPMC10394757
OpenAlexW4320896693

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.