Evidence map›Paper›PMID 33096480›Full record

ArticleEBioMedicine2020

Intra-tumour heterogeneity of diffuse large B-cell lymphoma involves the induction of diversified stroma-tumour interfaces.

Sabina Sangaletti, Fabio Iannelli, Federica Zanardi, Valeria Cancila, Paola Portararo, Laura Botti, Davide Vacca, Claudia Chiodoni, Arianna Di Napoli, Cesare Valenti and 7 more

Open access · goldAbstract read
In one paragraph

Article in EBioMedicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
5.2field-weighted citation impact, top 3% 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

23 citing papers in PubMed, 33 citations in OpenAlex.

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  18. A bone-based 3D scaffold as anFrontiers in oncology · 2022
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  20. Metabolic Swifts Govern Normal and Malignant B Cell Lymphopoiesis.International journal of molecular sciences · 2021
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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 6 institutions in 1 country.

Sabina SangalettiMolecular Immunology Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
Fabio IannelliBioinformatics Core Unit, IFOM, FIRC Institute of Molecular Oncology, Milan, Italy.
Federica ZanardiBioinformatics Core Unit, IFOM, FIRC Institute of Molecular Oncology, Milan, Italy.
Valeria CancilaTumor Immunology Unit, University of Palermo, Palermo, Italy.
Paola PortararoMolecular Immunology Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
Laura BottiMolecular Immunology Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
Davide VaccaTumor Immunology Unit, University of Palermo, Palermo, Italy.
Claudia ChiodoniMolecular Immunology Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
Arianna Di NapoliPathology Unit, Sapienza University of Rome, Sant'Andrea Hospital, Rome, Italy.
Cesare ValentiDepartment of Mathematics and Informatics, University of Palermo, Palermo, Italy.
Celeste RizzelloMolecular Immunology Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
Maria Carmela VeglianteHematology and Cell Therapy Unit, IRCCS-Istituto Tumori 'Giovanni Paolo II', Bari, Italy.
Federica PisatiTumor and Microenvironment Histopathology Unit, IFOM, FIRC Institute of Molecular Oncology, Milan, Italy.
Alessandro GulinoTumor Immunology Unit, University of Palermo, Palermo, Italy.
Maurilio PonzoniPathology Unit, IRCCS San Raffaele Scientific Institute, Vita-Salute San Raffaele University Milan, Milan, Italy.
Mario Paolo ColomboMolecular Immunology Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy. Electronic address: mariopaolo.colombo@istitutotumori.mi.it.
Claudio TripodoTumor Immunology Unit, University of Palermo, Palermo, Italy; Tumor and Microenvironment Histopathology Unit, IFOM, FIRC Institute of Molecular Oncology, Milan, Italy. Electronic address: claudio.tripodo@unipa.it.
Fondazione IRCCS Istituto Nazionale dei Tumori · ITIFOM · ITUniversity of Palermo · ITIstituto Tumori Bari · ITSapienza University of Rome · ITVita-Salute San Raffaele University · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundIntra-tumour heterogeneity in lymphoid malignancies encompasses selection of genetic events and epigenetic regulation of transcriptional programs. Clonal-related neoplastic cell populations are unsteadily subjected to immune editing and metabolic adaptations within different tissue microenvironments. How tissue-specific mesenchymal cells impact on the diversification of aggressive lymphoma clones is still unknown.

methodsCombining in situ quantitative immunophenotypical analyses and RNA sequencing we investigated the intra-tumour heterogeneity and the specific mesenchymal modifications that are associated with A20 diffuse large B-cell lymphoma (DLBCL) cells seeding of different tissue microenvironments. Furthermore, we characterized features of lymphoma-associated stromatogenesis in human DLBCL samples using Digital Spatial Profiling, and established their relationship with prognostically relevant variables, such as MYC.

findingsWe found that the tissue microenvironment casts a relevant influence over A20 transcriptional landscape also impacting on Myc and DNA damage response programs. Extending the investigation to mice deficient for the matricellular protein SPARC, a stromal prognostic factor in human DLBCL, we demonstrated a different immune imprint on A20 cells according to stromal Sparc proficiency. Through Digital Spatial Profiling of 87 immune and stromal genes on human nodal DLBCL regions characterized by different mesenchymal composition, we demonstrate intra-lesional heterogeneity arising from diversified mesenchymal contextures and impacting on the stromal and immune milieu.

interpretationOur study provides experimental evidence that stromal microenvironment generates topological determinants of intra-tumour heterogeneity in DLBCL involving key transcriptional pathways such as Myc expression, damage response programs and immune checkpoints.

fundingThis study has been supported by the Italian Foundation for Cancer Research (AIRC) (grants 15999 and 22145 to C. Tripodo) and by the University of Palermo.

Indexed as

Biomarkers, TumorGenetic HeterogeneityAnimalsCell Line, TumorComputational BiologyDisease Models, AnimalGene Expression ProfilingGene Expression Regulation, NeoplasticHumansImmunophenotypingIn Situ HybridizationLymphoma, Large B-Cell, DiffuseMiceModels, BiologicalPhenotypePrognosisBiomarkers, TumorDiffuse large B-cell lymphomaDigital spatial profilingIntra-tumour heterogeneityMicroenvironmentSPARC

Identifiers

PMID33096480
PMCPMC7581880
OpenAlexW3094510264

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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.