Evidence map›Paper›PMID 33795387›Full record

ArticleJournal for immunotherapy of cancer2021

Multiparametric flow cytometry highlights B7-H3 as a novel diagnostic/therapeutic target in GD2neg/low neuroblastoma variants.

Alessandra Dondero, Martina Morini, Davide Cangelosi, Katia Mazzocco, Martina Serra, Grazia Maria Spaggiari, Gianluca Rotta, Annalisa Tondo, Franco Locatelli, Aurora Castellano and 7 more

Open access · goldAbstract readValidation Study
In one paragraph

Article in Journal for immunotherapy of cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
3.5field-weighted citation impact, top 6% 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

28 citing papers in PubMed, 45 citations in OpenAlex.

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  11. Targeting the myeloid microenvironment in neuroblastoma.Journal of experimental & clinical cancer research : CR · 2023
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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

17 authors at 4 institutions in 1 country.

Alessandra DonderoDepartment of Experimental Medicine, University of Genova, Genova, Italy.
Martina MoriniLaboratory of Molecular Biology, IRCCS Istituto Giannina Gaslini, Genova, Italy.
Davide CangelosiClinical Bioinformatic, IRCCS Istituto Giannina Gaslini, Genova, Italy.
Katia MazzoccoUOC Anatomia Patologica, IRCCS Istituto Giannina Gaslini, Genova, Italy.
Martina SerraLaboratory of Clinical and Experimental Immunology, IRCCS Istituto Giannina Gaslini, Genova, Italy.
Grazia Maria SpaggiariDepartment of Experimental Medicine, University of Genova, Genova, Italy.
Gianluca RottaBecton Dickinson Italia, S.p.a, Milano, Italy.
Annalisa TondoDepartment of Pediatric Oncology, Meyer Children's University Hospital, Firenze, Italy.
Franco LocatelliDepartment of Pediatric Hematology and Oncology, Bambino Gesu Pediatric Hospital, Roma, Italy.
Aurora CastellanoDepartment of Pediatric Hematology and Oncology, Bambino Gesu Pediatric Hospital, Roma, Italy.
Francesca ScuderiUOC Oncology, IRCCS Istituto Giannina Gaslini, Genova, Italy.
Angela Rita SementaUOC Anatomia Patologica, IRCCS Istituto Giannina Gaslini, Genova, Italy.
Alessandra EvaLaboratory of Molecular Biology, IRCCS Istituto Giannina Gaslini, Genova, Italy.
Massimo ConteUOC Oncology, IRCCS Istituto Giannina Gaslini, Genova, Italy.
Alberto GaraventaUOC Oncology, IRCCS Istituto Giannina Gaslini, Genova, Italy.
Cristina BottinoDepartment of Experimental Medicine, University of Genova, Genova, Italy cristina.bottino@unige.it.
Roberta CastriconiDepartment of Experimental Medicine, University of Genova, Genova, Italy.ORCID 0000-0003-2806-1115
Istituto Giannina Gaslini · ITUniversity of Genoa · ITBambino Gesù Children's Hospital · ITMeyer Children's Hospital · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundHigh-risk neuroblastomas (HR-NBs) are rare, aggressive pediatric cancers characterized by resistance to therapy and relapse in more than 30% of cases, despite using an aggressive therapeutic protocol including targeting of GD2. The mechanisms responsible for therapy resistance are unclear and might include the presence of GD2neg/low NB variants and/or the expression of immune checkpoint ligands such as B7-H3.

methodHere, we describe a multiparametric flow cytometry (MFC) combining the acquisition of 10

resultsNo false positive are detected, and MFC shows high sensitivity (0.0005%). Optimized MFC identifies CD45negCD56pos NB cells in 11 out of 12 (91.6%) of BM indicated as infiltrated by CA, 7 of which coexpress high levels of GD2 and B7-H3. MFC detects CD45negCD56posGD2neg/low NB variants expressing high surface levels of B7-H3 in two patients with HR-NB (stage M) diagnosed at 53 and 139 months of age. One of them has a non-MYCN amplified tumor with unusual THpos PHOX2Bneg phenotype, which relapsed 141 months post-diagnosis with BM infiltration and a humerus lesion. All GD2neg/low NB variants are detected in patients at relapse. Kaplan-Meier analysis highlights an interesting dichotomous prognostic value of MML5, ULBPs, PVR, B7-H6, and CD47, ligands involved in NB recognition by the immune system.

conclusionsOur study validates a sensitive MFC analysis providing information on GD2 and B7-H3 surface expression and allowing fast, specific and sensitive evaluation of BM tumor burden. With other routinely used diagnostic and prognostic tools, MFC can improve diagnosis, prognosis, orienting novel personalized treatments in patients with GD2low/neg NB, who might benefit from innovative therapies combining B7-H3 targeting.

Indexed as

Flow CytometryAdolescentB7 AntigensBiomarkers, TumorCell Line, TumorChildChild, PreschoolGangliosidesHumansInfantMaleNeuroblastomaPredictive Value of TestsProgression-Free SurvivalReproducibility of ResultsTime FactorsB7 AntigensBiomarkers, TumorCD276 protein, humanganglioside, GD2Gangliosidesantigensimmune evationimmunotherapyneoplasmneuroblastomatumor biomarkers

Identifiers

PMID33795387
PMCPMC8021887
OpenAlexW3140310152

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.