Evidence map›Paper›PMID 39266215›Full record

ArticleJournal for immunotherapy of cancer2024

Circumventing resistance within the Ewing sarcoma microenvironment by combinatorial innate immunotherapy.

Wen Luo, Hai Hoang, Hongwen Zhu, Katherine Miller, Xiaokui Mo, Shiori Eguchi, Meijuan Tian, Yanling Liao, Janet Ayello, Jeremy M Rosenblum and 6 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal for immunotherapy of cancer, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing 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

13 citing papers in PubMed.

  1. Article
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  3. CXCL10-induced chemotaxis ofMolecular therapy. Oncology · 2025
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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

16 authors.

Wen LuoDepartment of Pediatrics, New York Medical College, Valhalla, New York, USA.
Hai HoangDepartment of Pediatrics, New York Medical College, Valhalla, New York, USA.
Hongwen ZhuDepartment of Pediatrics, New York Medical College, Valhalla, New York, USA.
Katherine MillerThe Steve and Cindy Rasmussen Institute for Genomic Medicine, Columbus, Ohio, USA.
Xiaokui MoBiomedical Informatics, The Ohio State University, Columbus, Ohio, USA.
Shiori EguchiDepartment of Pediatrics, New York Medical College, Valhalla, New York, USA.
Meijuan TianDepartment of Pediatrics, New York Medical College, Valhalla, New York, USA.
Yanling LiaoDepartment of Pediatrics, New York Medical College, Valhalla, New York, USA.
Janet AyelloDepartment of Pediatrics, New York Medical College, Valhalla, New York, USA.
Jeremy M RosenblumDepartment of Pediatrics, New York Medical College, Valhalla, New York, USA.
Mario MarcondesNektar Therapeutics, San Francisco, California, USA.
Mark CurrierThe Steve and Cindy Rasmussen Institute for Genomic Medicine, Columbus, Ohio, USA.
Elaine MardisThe Steve and Cindy Rasmussen Institute for Genomic Medicine, Columbus, Ohio, USA.
Timothy CripePediatric Hem/Onc/BMT, Nationwide Children's Hospital Hematology Oncology and Blood and Marrow Transplant, Columbus, Ohio, USA.ORCID http://orcid.org/0000-0002-8595-3577
Dean LeePediatric Hem/Onc/BMT, Nationwide Children's Hospital Hematology Oncology and Blood and Marrow Transplant, Columbus, Ohio, USA.ORCID http://orcid.org/0000-0001-6693-5392
Mitchell S CairoDepartment of Pediatrics, New York Medical College, Valhalla, New York, USA mitchell_cairo@nymc.edu.ORCID http://orcid.org/0000-0002-2075-434X

Funding

Project 4:Targeting M2-like Macrophages and MDSC with Myelolytic-VirotherapyU54CA232561 · NCI · RESEARCH INST NATIONWIDE CHILDREN'S HOSP · PI CASSADY, KEVIN A, CRIPE, TIMOTHY P · 2019 to 2023
$12.1M
NCI NIH HHS U54 CA232561
6 · The paper itself

Abstract

backgroundPediatric patients with recurrent/metastatic Ewing sarcoma (ES) have a dismal 5-year survival. Novel therapeutic approaches are desperately needed. Natural killer (NK) cell number and function are low in ES patient tumors, in large part due to the immunosuppressive tumor microenvironment (TME). Melanoma cell adhesion molecule (MCAM) is highly expressed on ES and associated with ES metastasis. NKTR-255 is a polymer-conjugated recombinant human interleukin-15 (IL-15) agonist improving NK cell activity and persistence. Magrolimab (MAG) is a CD47 blockade that reactivates the phagocytic activity of macrophages.

methodsTranscriptome profiling coupled with CIBERSORT analyses in both ES mouse xenografts and human patient tumors were performed to identify mechanisms of NK resistance in ES TME. A chimeric antigen receptor (CAR) NK cell targeting MCAM was engineered by CAR mRNA electroporation into ex vivo expanded NK cells. In vitro cytotoxicity assays were performed to investigate the efficacy of anti-MCAM-CAR-NK cell alone or combined with NKTR-255 against ES cells. Interferon-γ and perforin levels were measured by ELISA. The effect of MAG on macrophage phagocytosis of ES cells was evaluated by in vitro phagocytosis assays. Cell-based and patient-derived xenograft (PDX)-based xenograft mouse models of ES were used to investigate the antitumor efficacy of CAR-NK alone and combined with NKTR-255 and MAG in vivo.

resultsWe found that NK cell infiltration and activity were negatively regulated by tumor-associated macrophages (TAM) in ES TME. Expression of anti-MCAM CAR significantly and specifically enhanced NK cytotoxic activity against MCAM

conclusionsOur preclinical studies demonstrate that immunotherapy via the innate immune system by combining tumor-targeting CAR-NK cells with an IL-15 agonist and a CD47 blockade is a promising novel therapeutic approach to targeting MCAM

Indexed as

ImmunotherapySarcoma, EwingTumor MicroenvironmentAnimalsCell Line, TumorHumansImmunity, InnateKiller Cells, NaturalMiceXenograft Model Antitumor AssaysChimeric antigen receptor - CARMacrophageNatural killer - NKTumor microenvironment - TME

Identifiers

PMID39266215
PMCPMC11404285

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.