Evidence map›Paper›PMID 38562878›Full record

ArticleResearch square2024

Germinal Center Dark Zone harbors ATR-dependent determinants of T-cell exclusion that are also identified in aggressive lymphoma.

Valeria Cancila, Gaia Morello, Giorgio Bertolazzi, Allison Si-Yu Chan, Giulia Bastianello, Daniel Paysan, Patrick William Jaynes, Giovanna Schiavoni, Fabrizio Mattei, Silvia Piconese and 25 more

Open access · greenAbstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in Research square, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed, 1 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

35 authors at 16 institutions in 5 countries.

Valeria CancilaTumor Immunology Unit, Department of Health Sciences, University of Palermo, Palermo, Italy.
Gaia MorelloTumor Immunology Unit, Department of Health Sciences, University of Palermo, Palermo, Italy.
Giorgio BertolazziTumor Immunology Unit, Department of Health Sciences, University of Palermo, Palermo, Italy.
Allison Si-Yu ChanCancer Science Institute of Singapore, National University of Singapore, Singapore.
Giulia BastianelloIFOM ETS, The AIRC Institute of Molecular Oncology, Milan, Italy.
Daniel PaysanLaboratory for Nanoscale Biology, Paul Scherrer Institute, Villigen, Switzerland.ORCID 0000-0003-4995-7527
Patrick William JaynesCancer Science Institute of Singapore, National University of Singapore, Singapore.
Giovanna SchiavoniDepartment of Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
Fabrizio MatteiDepartment of Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.ORCID 0000-0002-5357-7773
Silvia PiconeseDepartment of Internal Clinical Sciences, Anesthesiology and Cardiovascular Sciences, Sapienza University of Rome, Rome, Italy.
Maria V RevueltaDivision of Hematology and Oncology, Medicine Department, Weill Cornell Medicine and NewYork-Presbyterian Hospital, New York.ORCID 0000-0002-7922-0713
Francesco NotoDepartment of Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
Adele De NinnoInstitute for Photonics and Nanotechnologies, Italian National Research Council, Rome, Italy.
Ilenia CammarataDepartment of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy; Neuroimmunology Unit, IRCCS Fondazione Santa Lucia, Rome, Italy.
Fabio PagniDepartment of Medicine and Surgery, Pathology, IRCCS Fondazione San Gerardo dei Tintori, University of Milano-Bicocca, Italy.
Saradha VenkatachalapathyLaboratory for Nanoscale Biology, Paul Scherrer Institute, Villigen, Switzerland.
Sabina SangalettiMolecular Immunology Unit, Department of Experimental Oncology, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
Arianna Di NapoliPathology Unit, Department of Clinical and Molecular Medicine, Sant'Andrea University Hospital, Sapienza University of Rome, Rome, Italy.
Davide VaccaTumor Immunology Unit, Department of Health Sciences, University of Palermo, Palermo, Italy.
Silvia LonardiPathology Unit, ASST Spedali Civili di Brescia, Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
Luisa LorenziPathology Unit, ASST Spedali Civili di Brescia, Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
Andrés J M FerreriLymphoma Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Beatrice BelmonteTumor Immunology Unit, Department of Health Sciences, University of Palermo, Palermo, Italy.
Gabriele VaranoIFOM ETS, The AIRC Institute of Molecular Oncology, Milan, Italy.
Mario Paolo ColomboMolecular Immunology Unit, Department of Experimental Oncology, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
Silvio BicciatoDepartment of Molecular Medicine, University of Padova, Padova, Italy.ORCID 0000-0002-1944-7078
Giorgio InghiramiPathology and Laboratory Medicine Department, Weill Cornell Medicine and New York-Presbyterian Hospital, New York.
Leandro CerchiettiDivision of Hematology and Oncology, Medicine Department, Weill Cornell Medicine and NewYork-Presbyterian Hospital, New York.
Maurilio PonzoniVita-Salute San Raffaele University, Milan, Italy.
Roberta ZappasodiDepartment of Medicine, Weill Cornell, New York, NY, USA.
Fabio FacchettiPathology Unit, ASST Spedali Civili di Brescia, Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
Marco FoianiIFOM ETS, The AIRC Institute of Molecular Oncology, Milan, Italy.
Stefano CasolaIFOM ETS, The AIRC Institute of Molecular Oncology, Milan, Italy.
Anand D JeyasekharanCancer Science Institute of Singapore, National University of Singapore, Singapore.
Claudio TripodoTumor Immunology Unit, Department of Health Sciences, University of Palermo, Palermo, Italy.
IFOM · ITUniversity of Palermo · ITBrescia University · USIstituto Superiore di Sanità · ITNational University of Singapore · SGNewYork–Presbyterian Hospital · USFondazione IRCCS Istituto Nazionale dei Tumori · ITPaul Scherrer Institute · CHVita-Salute San Raffaele University · ITCornell University · USFondazione Santa Lucia · ITIstituto Pasteur · ITNational Research Council · ROSapienza University of Rome · ITUniversity of Milano-Bicocca · ITUniversity of Padua · IT

Funding

Role of the stromal microenvironment in B-cell lymphoma progression and immune escapeR01CA242069 · NCI · WEILL MEDICAL COLL OF CORNELL UNIV · PI CERCHIETTI, LEANDRO C · 2020 to 2024
$2.9M
NCI NIH HHS R01 CA242069
6 · The paper itself

Abstract

The germinal center (GC) dark zone (DZ) and light zone (LZ) regions spatially separate expansion and diversification from selection of antigen-specific B-cells to ensure antibody affinity maturation and B cell memory. The DZ and LZ differ significantly in their immune composition despite the lack of a physical barrier, yet the determinants of this polarization are poorly understood. This study provides novel insights into signals controlling asymmetric T-cell distribution between DZ and LZ regions. We identify spatially-resolved DNA damage response and chromatin compaction molecular features that underlie DZ T-cell exclusion. The DZ spatial transcriptional signature linked to T-cell immune evasion clustered aggressive Diffuse Large B-cell Lymphomas (DLBCL) for differential T cell infiltration. We reveal the dependence of the DZ transcriptional core signature on the ATR kinase and dissect its role in restraining inflammatory responses contributing to establishing an immune-repulsive imprint in DLBCL. These insights may guide ATR-focused treatment strategies bolstering immunotherapy in tumors marked by DZ transcriptional and chromatin-associated features.

Identifiers

PMID38562878
PMCPMC10984086
OpenAlexW4392927882

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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.