Evidence map›Paper›PMID 39695851›Full record

ArticleJournal of hematology & oncology2024

Tumor-derived G-CSF induces an immunosuppressive microenvironment in an osteosarcoma model, reducing response to CAR.GD2 T-cells.

Michele Pezzella, Concetta Quintarelli, Maria C Quadraccia, Andrea Sarcinelli, Simona Manni, Laura Iaffaldano, Alessio Ottaviani, Roselia Ciccone, Antonio Camera, Maria L D'Amore and 20 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of hematology & oncology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed, 2 pooled it
–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

24 citing papers in PubMed, 2 syntheses or guidelines pooled it.

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  14. CAR-T cell immunotherapy in rhabdomyosarcoma.Journal of translational medicine · 2026
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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

30 authors.

Michele Pezzella *Department of Onco-Haematology and Cell and Gene Therapy, Bambino Gesù Children's Hospital, IRCCS, San Paolo N°15 Street, 00146, Rome, Italy.
Concetta Quintarelli *Department of Onco-Haematology and Cell and Gene Therapy, Bambino Gesù Children's Hospital, IRCCS, San Paolo N°15 Street, 00146, Rome, Italy.
Maria C QuadracciaDepartment of Onco-Haematology and Cell and Gene Therapy, Bambino Gesù Children's Hospital, IRCCS, San Paolo N°15 Street, 00146, Rome, Italy.
Andrea SarcinelliDepartment of Onco-Haematology and Cell and Gene Therapy, Bambino Gesù Children's Hospital, IRCCS, San Paolo N°15 Street, 00146, Rome, Italy.
Simona ManniDepartment of Onco-Haematology and Cell and Gene Therapy, Bambino Gesù Children's Hospital, IRCCS, San Paolo N°15 Street, 00146, Rome, Italy.
Laura IaffaldanoDepartment of Onco-Haematology and Cell and Gene Therapy, Bambino Gesù Children's Hospital, IRCCS, San Paolo N°15 Street, 00146, Rome, Italy.
Alessio OttavianiDepartment of Onco-Haematology and Cell and Gene Therapy, Bambino Gesù Children's Hospital, IRCCS, San Paolo N°15 Street, 00146, Rome, Italy.
Roselia CicconeDepartment of Onco-Haematology and Cell and Gene Therapy, Bambino Gesù Children's Hospital, IRCCS, San Paolo N°15 Street, 00146, Rome, Italy.
Antonio CameraDepartment of Onco-Haematology and Cell and Gene Therapy, Bambino Gesù Children's Hospital, IRCCS, San Paolo N°15 Street, 00146, Rome, Italy.
Maria L D'AmoreDepartment of Onco-Haematology and Cell and Gene Therapy, Bambino Gesù Children's Hospital, IRCCS, San Paolo N°15 Street, 00146, Rome, Italy.
Stefano Di CeccaDepartment of Onco-Haematology and Cell and Gene Therapy, Bambino Gesù Children's Hospital, IRCCS, San Paolo N°15 Street, 00146, Rome, Italy.
Matilde SinibaldiDepartment of Onco-Haematology and Cell and Gene Therapy, Bambino Gesù Children's Hospital, IRCCS, San Paolo N°15 Street, 00146, Rome, Italy.
Marika GuercioDepartment of Onco-Haematology and Cell and Gene Therapy, Bambino Gesù Children's Hospital, IRCCS, San Paolo N°15 Street, 00146, Rome, Italy.
Mariasole AurigemmaDepartment of Onco-Haematology and Cell and Gene Therapy, Bambino Gesù Children's Hospital, IRCCS, San Paolo N°15 Street, 00146, Rome, Italy.
Pamela De FalcoDepartment of Onco-Haematology and Cell and Gene Therapy, Bambino Gesù Children's Hospital, IRCCS, San Paolo N°15 Street, 00146, Rome, Italy.
Valentina FustainoDepartment of Onco-Haematology and Cell and Gene Therapy, Bambino Gesù Children's Hospital, IRCCS, San Paolo N°15 Street, 00146, Rome, Italy.
Rossella RotaDepartment of Onco-Haematology and Cell and Gene Therapy, Bambino Gesù Children's Hospital, IRCCS, San Paolo N°15 Street, 00146, Rome, Italy.
Silvia PomellaDepartment of Onco-Haematology and Cell and Gene Therapy, Bambino Gesù Children's Hospital, IRCCS, San Paolo N°15 Street, 00146, Rome, Italy.
Matteo CassandriDepartment of Onco-Haematology and Cell and Gene Therapy, Bambino Gesù Children's Hospital, IRCCS, San Paolo N°15 Street, 00146, Rome, Italy.
Angela Di GiannataleDepartment of Onco-Haematology and Cell and Gene Therapy, Bambino Gesù Children's Hospital, IRCCS, San Paolo N°15 Street, 00146, Rome, Italy.
Chiara AgratiUnit of Pathogen Specific Immunity, Bambino Gesù Children's Hospital, IRCCS, 00145, Rome, Italy.
Veronica BordoniUnit of Pathogen Specific Immunity, Bambino Gesù Children's Hospital, IRCCS, 00145, Rome, Italy.
Federica GuarracinoUnit of Pathogen Specific Immunity, Bambino Gesù Children's Hospital, IRCCS, 00145, Rome, Italy.
Michele MassaDepartment of Onco-Haematology and Cell and Gene Therapy, Bambino Gesù Children's Hospital, IRCCS, San Paolo N°15 Street, 00146, Rome, Italy.
Giada Del BaldoDepartment of Onco-Haematology and Cell and Gene Therapy, Bambino Gesù Children's Hospital, IRCCS, San Paolo N°15 Street, 00146, Rome, Italy.
Marco BecilliDepartment of Onco-Haematology and Cell and Gene Therapy, Bambino Gesù Children's Hospital, IRCCS, San Paolo N°15 Street, 00146, Rome, Italy.
Giuseppe M MilanoDepartment of Onco-Haematology and Cell and Gene Therapy, Bambino Gesù Children's Hospital, IRCCS, San Paolo N°15 Street, 00146, Rome, Italy.
Francesca Del BufaloDepartment of Onco-Haematology and Cell and Gene Therapy, Bambino Gesù Children's Hospital, IRCCS, San Paolo N°15 Street, 00146, Rome, Italy.
Franco Locatelli *Department of Onco-Haematology and Cell and Gene Therapy, Bambino Gesù Children's Hospital, IRCCS, San Paolo N°15 Street, 00146, Rome, Italy. franco.locatelli@opbg.net.
Biagio De Angelis *Department of Onco-Haematology and Cell and Gene Therapy, Bambino Gesù Children's Hospital, IRCCS, San Paolo N°15 Street, 00146, Rome, Italy. biagio.deangelis@opbg.net.

Funding

Alleanza Contro il Cancro Grant Rete ACC RCR-2022-23682287 Preclinical Models (BDA)Associazione Italiana Ricerca per la Ricerca sul Cancro AIRC-Special Project 5×1000 no. 9962 (FL)Associazione Italiana Ricerca per la Ricerca sul Cancro Investigator Grant AIRC IG 2018 id. 21724 (FL)Associazione Italiana Ricerca per la Ricerca sul Cancro Investigator Grant AIRC-IG ID. 29057 (BDA)IMI JU/T2EVOLVE grant number 945393 (FL)Ministero della Salute Progetto Ministeriale CAR-T (FL)Ministero della Salute Ricerca Corrente 5X1000 (BDA)Ministero della Salute Ricerca Finalizzata GR-2013-02359212 (CQ)Ministry of Health and Alleanza Contro il Cancro-Working Group Sarcoma ACC-WG Sarcoma (FL)PNRR CN3 "National Center for Gene Therapy and Drugs based on RNA Technology" (F. L.) European Union - Next Generation EU, Mission 4, Component 2, CUP B93D21010860004
6 · The paper itself

Abstract

Sarcomas are rare, mesenchymal tumors, representing about 10-15% of all childhood cancers. GD2 is a suitable target for chimeric antigen receptor (CAR) T-cell therapy due to its overexpression in several solid tumors. In this preclinical study, we investigated the potential use of iCasp9.2A.GD2.CAR-CD28.4-1BBζ (CAR.GD2) T-cells as a treatment option for patients who have GD2-positive sarcomas and we sought to identify factors shaping hostile tumor microenvironment in this setting. GD2 expression was evaluated by flow-cytometry on primary tumor biopsies of pediatric sarcoma patients. GD2 expression in sarcoma cells was also evaluated in response to an enhancer of zeste homolog 2 (EZH2) inhibitor (Tazemetostat). The antitumor activity of CAR.GD2 T-cells was evaluated both in vitro and in vivo preclinical models of orthotopic and/or metastatic soft-tissue and bone sarcomas. GD2 expression was detected in 55% of the primary tumors. Notably, the Osteosarcoma and Alveolar Rhabdomyosarcomas subtypes exhibited the highest GD2 expression levels, while Ewing sarcoma showed the lowest. CAR.GD2 T-cells show a significant tumor control both in vitro and in vivo models of GD2-expressing tumors. Pretreatment with an EZH2 inhibitor (Tazemetostat) upregulating GD2 expression, sensitizes GD2

Indexed as

OsteosarcomaReceptors, Chimeric AntigenTumor MicroenvironmentAnimalsBenzamidesBiphenyl CompoundsBone NeoplasmsCell Line, TumorFemaleGangliosidesHumansImmunotherapy, AdoptiveMiceMice, SCIDMorpholinesPyridonesBenzamidesBiphenyl Compoundsganglioside, GD2GangliosidesMorpholinesPyridonesReceptors, Chimeric AntigentazemetostatCAR.GD2 T-cellsChimeric antigen receptor (CAR)CXCL8EZH2 inhibitorG-CSFGD2ICasp9.2A.GD2.CAR-CD28.4–1BBζMyeloid-derived suppressor cellsSarcoma

Identifiers

PMID39695851
PMCPMC11656657

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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.