Evidence map›Paper›PMID 40658105›Full record

ArticleThe Journal of experimental medicine2025

Myeloid-targeting immunotherapies overcome inhibitory barriers in immune-evasive neuroblastoma.

Marie Ménard, Hiroyuki Yoda, Nicole Nasholm, Megumi J Barata, Linyu Wang, Erin F Simonds, Edbert D Lu, Shannon Wong-Michalak, Lauren McHenry, Alvin Farrel and 10 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of experimental medicine, 2025. 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.

  1. Review
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

20 authors.

Marie Ménard *Department of Neurology, University of California, San Francisco, CA, USA.ORCID 0000-0003-1511-4361
Hiroyuki Yoda *Department of Neurology, University of California, San Francisco, CA, USA.ORCID 0000-0002-5528-8940
Nicole NasholmDepartment of Neurology, University of California, San Francisco, CA, USA.ORCID 0000-0002-5451-4985
Megumi J BarataDepartment of Neurology, University of California, San Francisco, CA, USA.ORCID 0009-0002-1032-3113
Linyu WangDepartment of Neurology, University of California, San Francisco, CA, USA.ORCID 0009-0008-4952-4426
Erin F SimondsDepartment of Neurology, University of California, San Francisco, CA, USA.ORCID 0000-0002-3497-4861
Edbert D LuDepartment of Neurology, University of California, San Francisco, CA, USA.ORCID 0000-0003-1411-6584
Shannon Wong-MichalakDepartment of Neurology, University of California, San Francisco, CA, USA.ORCID 0000-0002-6932-6039
Lauren McHenryDepartment of Neurology, University of California, San Francisco, CA, USA.ORCID 0009-0002-2692-049X
Alvin FarrelDivision of Oncology and Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA, USA.ORCID 0000-0003-1942-5992
Rebecca KaufmanDivision of Oncology and Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA, USA.ORCID 0000-0001-8535-9730
Vanessa LopezChildren's Hospital Los Angeles, Cancer and Blood Disease Institutes, and The Saban Research Institute , Los Angeles, CA, USA.ORCID 0000-0002-8340-5411
Rebekah J KennedyChildren's Hospital Los Angeles, Cancer and Blood Disease Institutes, and The Saban Research Institute , Los Angeles, CA, USA.ORCID 0000-0002-5613-4230
G Esteban FernandezChildren's Hospital Los Angeles, Cancer and Blood Disease Institutes, and The Saban Research Institute , Los Angeles, CA, USA.ORCID 0000-0002-8393-9229
Hiroyuki ShimadaDepartments of Pathology and Pediatrics, Stanford University, Stanford, CA, USA.ORCID 0000-0001-5025-7507
Liron D GrossmannSheba Medical Center , Ramat-Gan, Israel.ORCID 0000-0002-0692-8921
Shahab AsgharzadehChildren's Hospital Los Angeles, Cancer and Blood Disease Institutes, and The Saban Research Institute , Los Angeles, CA, USA.ORCID 0000-0002-0510-3848
John M MarisDivision of Oncology and Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA, USA.ORCID 0000-0002-8088-7929
W Clay GustafsonDepartment of Pediatrics, University of California, San Francisco, CA, USA.ORCID 0000-0002-1812-5675
William A WeissDepartment of Neurology, University of California, San Francisco, CA, USA.ORCID 0000-0003-2230-9132

Funding

Translational InformaticsP30CA082103 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Alan Ashworth · 1999 to 2026
$209.7M
Tumor microenvironment-dependent therapy resistanceP01CA217959 · NCI · CHILDREN'S HOSP OF PHILADELPHIA · PI Kimberly Stegmaier · 2017 to 2026
$20.7M
Integrating targeted and immunotherapy to treat genetically heterogeneous cancersU01CA217864 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI BALMAIN, ALLAN, KRUMMEL, MATTHEW F · 2017 to 2021
$5.1M
Remodeling the translatome in N-myc mediated medulloblastoma and its therapeutic implicationsR01NS125668 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Davide Ruggero, WILLIAM A WEISS · 2022 to 2026
$3.3M
Alex's Lemonade Stand FoundationCancer Research UKEfim Guzik chairNational Cancer CenterNCI NIH HHS P01 CA217959NCI NIH HHS P30 CA082103NCI NIH HHS U01 CA217864NIH HHS P01CA217959NIH HHS P30CA82103NIH HHS R01NS125668NIH HHS U01CA217864NINDS NIH HHS R01 NS125668St. Baldrick's FoundationUehara Memorial FoundationU.S. Department of Defense CA170257P1
6 · The paper itself

Abstract

Neuroblastomas are highly heterogeneous tumors originating from neural crest-derived cells destined to form the sympathetic nervous system. Nearly half of high-risk tumors present with amplification of the MYCN proto-oncogene. Here, we describe a Mycn-driven, transplantable, non-germline, genetically engineered mouse model (Mycn-nGEMM). Mycn-nGEMM tumors recapitulate the immune-evasive, macrophage-rich tumor microenvironment of high-risk, MYCN-amplified human neuroblastoma. Treatment of tumor-bearing mice with anti-PD-L1, but not anti-PD-1 or anti-CTLA-4, inhibited tumor growth, profoundly remodeling the tumor microenvironment by depleting anti-inflammatory macrophages and increasing T cell infiltration. Surprisingly, while tumor cells showed low expression of PD-L1, anti-inflammatory macrophages from both murine and human neuroblastoma expressed PD-L1. We identified cytokines, including macrophage migration inhibitory factor, secreted by the Mycn-nGEMM cancer cells that drive expression of PD-L1 on macrophages. Combining anti-PD-L1 with CD40 agonist antibodies further improved survival in Mycn-nGEMM mice, demonstrating the potential for myeloid-targeting immunotherapies to overcome inhibitory barriers in immune-evasive neuroblastoma.

Indexed as

ImmunotherapyMyeloid CellsNeuroblastomaAnimalsB7-H1 AntigenCD40 AntigensCell Line, TumorDisease Models, AnimalHumansMacrophagesMiceMice, TransgenicN-Myc Proto-Oncogene ProteinProto-Oncogene MasTumor MicroenvironmentB7-H1 AntigenCD40 AntigensMAS1 protein, humanN-Myc Proto-Oncogene ProteinProto-Oncogene Mas

Identifiers

PMID40658105
PMCPMC12263170

What OpenQuestion holds

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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.