Evidence map›Paper›PMID 36397148›Full record

ArticleJournal of experimental & clinical cancer research : CR2022

Combined mitoxantrone and anti-TGFβ treatment with PD-1 blockade enhances antitumor immunity by remodelling the tumor immune landscape in neuroblastoma.

Valeria Lucarini, Ombretta Melaiu, Silvia D'Amico, Fabio Pastorino, Patrizia Tempora, Marco Scarsella, Marco Pezzullo, Adele De Ninno, Valentina D'Oria, Michele Cilli and 10 more

Open access · goldAbstract read
In one paragraph

Article in Journal of experimental & clinical cancer research : CR, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
3.0field-weighted citation impact, top 7% 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

24 citing papers in PubMed, 26 citations in OpenAlex.

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  20. 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

20 authors at 7 institutions in 2 countries.

Valeria Lucarini *Department of Paediatric Haematology/Oncology and of Cell and Gene Therapy, Bambino Gesù Children's Hospital, IRCCS, 00146, Rome, Italy.
Ombretta Melaiu *Department of Paediatric Haematology/Oncology and of Cell and Gene Therapy, Bambino Gesù Children's Hospital, IRCCS, 00146, Rome, Italy.
Silvia D'AmicoDepartment of Paediatric Haematology/Oncology and of Cell and Gene Therapy, Bambino Gesù Children's Hospital, IRCCS, 00146, Rome, Italy.
Fabio PastorinoLaboratory of Experimental Therapies in Oncology, IRCCS Istituto Giannina Gaslini, 16147, Genoa, Italy.
Patrizia TemporaDepartment of Paediatric Haematology/Oncology and of Cell and Gene Therapy, Bambino Gesù Children's Hospital, IRCCS, 00146, Rome, Italy.
Marco ScarsellaFlow Cytometry Core Facility, Bambino Gesù Children's Hospital, IRCCS, 00146, Rome, Italy.
Marco PezzulloResearch Laboratories, Bambino Gesù Children's Hospital, IRCCS, 00146, Rome, Italy.
Adele De NinnoCNR Institute for Photonics and Nanotechnology, Rome, 00156, Italy.
Valentina D'OriaConfocal Microscopy Core Facility, Research Center, Bambino Gesù Children's Hospital, IRCCS, 00146, Rome, Italy.
Michele CilliIRCCS Ospedale Policlinico San Martino, Animal Facility, 16132, Genoa, Italy.
Laura EmioniteIRCCS Ospedale Policlinico San Martino, Animal Facility, 16132, Genoa, Italy.
Paola InfanteDepartment of Molecular Medicine, University La Sapienza, 00161, Rome, Italy.
Lucia Di MarcotullioDepartment of Molecular Medicine, University La Sapienza, 00161, Rome, Italy.
Maria Antonietta De IorisDepartment of Paediatric Haematology/Oncology and of Cell and Gene Therapy, Bambino Gesù Children's Hospital, IRCCS, 00146, Rome, Italy.
Giovanni BarillariDepartment of Clinical Sciences and Translational Medicine, University of Rome "Tor Vergata", Rome, Italy.
Rita AlaggioPathology Unit, Bambino Gesù Children's Hospital, IRCCS, 00146, Rome, Italy.
Luca BusinaroCNR Institute for Photonics and Nanotechnology, Rome, 00156, Italy.
Mirco PonzoniLaboratory of Experimental Therapies in Oncology, IRCCS Istituto Giannina Gaslini, 16147, Genoa, Italy.
Franco LocatelliDepartment of Paediatric Haematology/Oncology and of Cell and Gene Therapy, Bambino Gesù Children's Hospital, IRCCS, 00146, Rome, Italy.
Doriana FruciDepartment of Paediatric Haematology/Oncology and of Cell and Gene Therapy, Bambino Gesù Children's Hospital, IRCCS, 00146, Rome, Italy. doriana.fruci@opbg.net.ORCID http://orcid.org/0000-0003-3388-7296
Bambino Gesù Children's Hospital · ITCenter for Biomolecular Nanotechnologies · ITIstituto Giannina Gaslini · ITOspedale Policlinico San Martino · ITSapienza University of Rome · ITUniversity of Rome Tor Vergata · ITUniversità Cattolica del Sacro Cuore · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundPoor infiltration of functioning T cells renders tumors unresponsive to checkpoint-blocking immunotherapies. Here, we identified a combinatorial in situ immunomodulation strategy based on the administration of selected immunogenic drugs and immunotherapy to sensitize poorly T-cell-infiltrated neuroblastoma (NB) to the host antitumor immune response.

methods975A2 and 9464D NB cell lines derived from spontaneous tumors of TH-MYCN transgenic mice were employed to study drug combinations able of enhancing the antitumor immune response using in vivo and ex vivo approaches. Migration of immune cells towards drug-treated murine-derived organotypic tumor spheroids (MDOTS) were assessed by microfluidic devices. Activation status of immune cells co-cultured with drug-treated MDOTS was evaluated by flow cytometry analysis. The effect of drug treatment on the immune content of subcutaneous or orthotopic tumors was comprehensively analyzed by flow-cytometry, immunohistochemistry and multiplex immunofluorescence. The chemokine array assay was used to detect soluble factors released into the tumor microenvironment. Patient-derived organotypic tumor spheroids (PDOTS) were generated from human NB specimens. Migration and activation status of autologous immune cells to drug-treated PDOTS were performed.

resultsWe found that treatment with low-doses of mitoxantrone (MTX) recalled immune cells and promoted CD8

conclusionsCombined treatment with low-dose of MTX and anti-TGFβ treatment with PD-1 blockade improves antitumor immunity by remodelling the tumor immune landscape and overcoming the immunosuppressive microenvironment of aggressive NB.

Indexed as

NeuroblastomaProgrammed Cell Death 1 ReceptorAnimalsCD8-Positive T-LymphocytesCell Line, TumorHumansMiceMice, TransgenicMitoxantroneTransforming Growth Factor betaTumor MicroenvironmentMitoxantroneProgrammed Cell Death 1 ReceptorTransforming Growth Factor betaDrug EvaluationImmunomodulationImmunotherapyNeuroblastomaTumor Microenvironment

Identifiers

PMID36397148
PMCPMC9670422
OpenAlexW4309170407

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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.