Evidence map›Paper›PMID 38234841›Full record

ArticleResearch square2023

Wnt inhibition alleviates resistance to immune checkpoint blockade in glioblastoma.

Rakesh Jain, Shanmugarajan Krishnan, Somin Lee, Zohreh Amoozgar, Sonu Subudhi, Ashwin Kumar, Jessica Posada, Neal Lindeman, Pinji Lei, Mark Duquette and 6 more

Open access · greenAbstract readPreprint
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. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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.

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

1 citing paper in PubMed, 3 citations in OpenAlex.

  1. 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

16 authors at 2 institutions in 1 country.

Shanmugarajan KrishnanMGH.
Zohreh AmoozgarMGH.
Sonu SubudhiMassachusetts General Hospital.
Ashwin KumarMGH.
Jessica PosadaMGH.
Neal LindemanBrigham and Women's Hospital.
Pinji LeiMGH.
Mark DuquetteMGH.
Sylvie RobergeMGH.
Peigen HuangMGH.
Patrik AnderssonMGH.
Dai FukumuraMassachusetts General Hospital.ORCID 0000-0002-9505-4444
Brigham and Women's Hospital · USMarion General Hospital · US

Funding

VASCULAR, PULMONARY AND RENAL INJURYT32HL007627 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI GIMBRONE, MICHAEL A, MITCHELL, RICHARD N · 1985 to 2019
$12.7M
Dissecting Pediatric Brain Tumor Microenvironment to Improve TreatmentR35CA197743 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI JAIN, RAKESH K. · 2015 to 2020
$5.7M
Novel Developmental Pathways Underlying Psychiatric DisordersR01MH110438 · NIMH · MCLEAN HOSPITAL · PI Anju Vasudevan · 2016 to 2026
$4.7M
Targeting physical stress-driven mechanisms to overcome glioblastoma treatment resistanceU01CA261842 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI JAIN, RAKESH K., MUNN, LANCE L. · 2021 to 2025
$3.1M
Reprogramming PDAC tumor microenvironment to improve immunotherapyU01CA224348 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI BOUCHER, YVES, JAIN, RAKESH K. · 2017 to 2021
$2.9M
Oncopathology Training ProgramT32CA251062 · NCI · DANA-FARBER CANCER INST · PI JON C. ASTER, KATHLEEN H BURNS · 2020 to 2026
$2.4M
Improving treatment of HER2+ breast cancer brain metastasis by targeting lipid metabolismR01CA259253 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI JAIN, RAKESH K., VANDER HEIDEN, MATTHEW G. · 2021 to 2025
$2.3M
Reengineering obesity-induced abnormal microenvironment to improve PDAC treatmentR01CA208205 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI FUKUMURA, DAI, JAIN, RAKESH K. · 2017 to 2020
$2.2M
Reprogramming the Tumor Microenvironment to Improve Immunotherapy of Glioblastoma by Co-Targeting VEGF and Ang2R01NS118929 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI FUKUMURA, DAI · 2021 to 2025
$2.0M
Vascularized tumor explants for drug testingR01CA247441 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI MUNN, LANCE L. · 2021 to 2025
$1.9M
Novel Autonomous Roles of CNS AngiogenesisR01NS100808 · NINDS · MCLEAN HOSPITAL · PI VASUDEVAN, ANJU · 2017 to 2021
$1.7M
Targeting abnormal immunomechanics in the glioblastoma microenvironment to improve therapeutic responseK22CA258410 · NCI · UNIVERSITY OF NOTRE DAME · PI DATTA, MEENAL · 2021 to 2023
$573k
NCI NIH HHS K22 CA258410NCI NIH HHS R01 CA208205NCI NIH HHS R01 CA247441NCI NIH HHS R01 CA259253NCI NIH HHS R35 CA197743NCI NIH HHS T32 CA251062NCI NIH HHS U01 CA224348NCI NIH HHS U01 CA261842NHLBI NIH HHS T32 HL007627NIBIB NIH HHS R21 EB031982NIMH NIH HHS R01 MH110438NINDS NIH HHS R01 NS100808NINDS NIH HHS R01 NS118929
6 · The paper itself

Abstract

Wnt signaling plays a critical role in the progression and treatment outcome of glioblastoma (GBM). Here, we identified WNT7b as a heretofore unknown mechanism of resistance to immune checkpoint inhibition (αPD1) in GBM patients and murine models. Acquired resistance to αPD1 was found to be associated with the upregulation of Wnt7b and β-catenin protein levels in GBM in patients and in a clinically relevant, stem-rich GBM model. Combining the porcupine inhibitor WNT974 with αPD1 prolonged the survival of GBM-bearing mice. However, this combination had a dichotomous response, with a subset of tumors showing refractoriness. WNT974 and αPD1 expanded a subset of DC3-like dendritic cells (DCs) and decreased the granulocytic myeloid-derived suppressor cells (gMDSCs) in the tumor microenvironment (TME). By contrast, monocytic MDSCs (mMDSCs) increased, while T-cell infiltration remained unchanged, suggesting potential TME-mediated resistance. Our preclinical findings warrant the testing of Wnt7b/β-catenin combined with αPD1 in GBM patients with elevated Wnt7b/β-catenin signaling.

Identifiers

PMID38234841
PMCPMC10793505
OpenAlexW4390227146

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.